Mature osteoblasts that have become embedded in the BONE MATRIX. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.
The process of bone formation. Histogenesis of bone including ossification.
The inner and longer bone of the FOREARM.
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.
A circular structural unit of bone tissue. It consists of a central hole, the Haversian canal through which blood vessels run, surrounded by concentric rings, called lamellae.
The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.
Bone loss due to osteoclastic activity.
A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.
A parathyroid hormone receptor subtype that recognizes both PARATHYROID HORMONE and PARATHYROID HORMONE-RELATED PROTEIN. It is a G-protein-coupled receptor that is expressed at high levels in BONE and in KIDNEY.
Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.
A membrane-bound metalloendopeptidase that may play a role in the degradation or activation of a variety of PEPTIDE HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Genetic mutations that result in loss of function of this protein are a cause of HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT.
The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the FIBULA laterally, the TALUS distally, and the FEMUR proximally.
An abnormal hardening or increased density of bone tissue.
The SKELETON of the HEAD including the FACIAL BONES and the bones enclosing the BRAIN.
Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.
The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.
The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot.
X-RAY COMPUTERIZED TOMOGRAPHY with resolution in the micrometer range.
Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).
An alloy of 60% cobalt, 20% chromium, 5% molybdenum, and traces of other substances. It is used in dentures, certain surgical appliances, prostheses, implants, and instruments.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; and growth retardation. Autosomal and X-linked dominant and recessive variants have been reported.
A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.
A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.
The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth.

Multilineage potential of adult human mesenchymal stem cells. (1/546)

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.  (+info)

Hard fallow deer antler: a living bone till antler casting? (2/546)

Deer antlers are the only mammalian bone structures which regenerate completely every year. Once developed, antlers are cleaned of the velvet-like skin. Presently it is believed that due to velvet shedding the blood supply is interrupted in the solidifying antler bone. Histological examinations were made on different parts of fallow deer antlers investigated from the time of velvet shedding till the antler casting. The present study on hard (polished) antlers revealed living bone with regions presenting living osteocytes, active osteoblasts, osteoid seams and even early stages of trabecular microcallus formation, thus indicating to a continuous bone remodeling. A well developed vascular system was found despite the presence of hard antler bone. The pedicle bone exhibits a rich supply of capillaries and vessels connected to the spongy core of the main branch and the compact bone as well. There is evidence that hard fallow deer antlers possess a functioning vascular system that "keeps the antler moist" resulting in a high impact resistance when fights are most frequent. As late as 3 weeks prior to antler casting a large number of living cells were discovered within the antler core. As we have no doubt that parts of the polished fallow deer antler represent a living bone, we have concluded that a sufficient blood supply of the antler core is maintained almost till the time of antler casting by vessels passing through the antler base.  (+info)

Mechanotransduction in bone--role of the lacuno-canalicular network. (3/546)

The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Over the last several years significant progress has been made in this field, which we will try to summarize. These studies emphasize the role of osteocytes as the professional mechanosensory cells of bone, and the lacuno-canalicular porosity as the structure that mediates mechanosensing. Strain-derived flow of interstitial fluid through this porosity seems to mechanically activate the osteocytes, as well as ensuring transport of cell signaling molecules and nutrients and waste products. This concept allows an explanation of local bone gain and loss, as well as remodeling in response to fatigue damage, as processes supervised by mechanosensitive osteocytes.  (+info)

Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis. (4/546)

Alpha-mannosidosis is a lysosomal storage disease with autosomal recessive inheritance caused by a deficiency of the lysosomal alpha-mannosidase, which is involved in the degradation of asparagine-linked carbohydrate cores of glycoproteins. An alpha-mannosidosis mouse model was generated by targeted disruption of the gene for lysosomal alpha-mannosidase. Homozygous mutant animals exhibit alpha-mannosidase enzyme deficiency and elevated urinary secretion of mannose-containing oligosaccharides. Thin-layer chromatography revealed an accumulation of oligosaccharides in liver, kidney, spleen, testis and brain. The cellular alterations were characterized by multiple membrane-limited cytoplasmic vacuoles as seen for instance in liver, exocrine pancreas, kidney, thyroid gland, smooth muscle cells, osteocytes and in various neurons of the central and peripheral nervous systems. The morphological lesions and their topographical distribution, as well as the biochemical alterations, closely resemble those reported for human alpha-mannosidosis. This mouse model will be a valuable tool for studying the pathogenesis of inherited alpha-mannosidosis and may help to evaluate therapeutic approaches for lysosomal storage diseases.  (+info)

Histomorphological study on pattern of fluid movement in cortical bone in goats. (5/546)

Streaming potential is considered one of the most important mechanisms to moderate the function of osteoblasts and osteocytes in bone growth, remodeling and fracture repair. The present study was designed to demonstrate the fluid flow pattern in the cortical bone matrix in an animal model using undecalcified histological techniques. Immediately after injection of ferritin into the tibia nutrient artery of four adult goats, the animals were euthanized. Undecalcified transverse and longitudinal blocks of cortical bone obtained from the tibial diaphysis were immersed in Perl's reagent and embedded in methyl methacrylate. Sections were cut and ground to 30-50 microm thickness for histomorphological evaluation at different magnifications and focusing levels. A serial grinding technique was used to validate the observations made at different focusing levels. As expected, ferritin was observed in the interstitial compartment in both transverse and longitudinal sections. In osteons sectioned transversely, the pattern of centrifugal movement of ferritin marker was demonstrated as single or multiple halos around the Haversian canal. The most apparent halo in osteons with multiple halos was the one found closest to the Haversian canal. The total number of identifiable single or multiple halos increased or was altered when counting was made with higher magnification or at different focusing levels, respectively. Irregular and incomplete ferritin halos indicated structural complexity of the osteons. Overall, the pattern of ferritin movement was consistent with bulk interstitial fluid flow influenced by both hydrostatic pressure and transudation. This study demonstrated for the first time multiple concentric halos of the fluid flow marker ferritin around Haversian canals in the cortical interstitial compartment. The results suggest that the undecalcified technique might be a useful method for qualitative and quantitative studies on cortical fluid flow.  (+info)

Histological analysis and ancient DNA amplification of human bone remains found in caius iulius polybius house in pompeii. (6/546)

Thirteen skeletons found in the Caius Iulius Polybius house, which has been the object of intensive study since its discovery in Pompeii 250 years ago, have provided an opportunity to study either bone diagenesis by histological investigation or ancient DNA by polymerase chain reaction analysis. DNA analysis was done by amplifying both X- and Y-chromosomes amelogenin loci and Y-specific alphoid repeat locus. The von Willebrand factor (vWF) microsatellite locus on chromosome 12 was also analyzed for personal identification in two individuals showing alleles with 10/11 and 12/12 TCTA repeats, respectively. Technical problems were the scarcity of DNA content from osteocytes, DNA molecule fragmentation, microbial contamination which change bone structure, contaminating human DNA which results from mishandling, and frequent presence of Taq DNA polymerase inhibiting molecules like polyphenols and heavy metals. The results suggest that the remains contain endogenous human DNA that can be amplified and analyzed. The amplifiability of DNA corresponds to the bone preservation and dynamics of the burial conditions subsequent to the 79 A.D. eruption.  (+info)

Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. (7/546)

The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis - the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.  (+info)

Osteocyte hypoxia: a novel mechanotransduction pathway. (8/546)

Bone is a unique tissue in which to examine mechanotransduction due to its essential role in weight bearing. Within bone, the osteocyte is an ideal cellular mechanotransducer candidate. Because osteocytes reside distant from the blood supply, their metabolic needs are met by a combination of passive diffusion and enhanced diffusion, arising when the tissue is loaded during functional activity. Therefore, we hypothesized that depriving a bone of mechanical loading (and thus eliminating diffusion enhanced by loading) would rapidly induce osteocyte hypoxia. Using the avian ulna model of disuse osteopenia, we found that 24 h of unloading results in significant osteocyte hypoxia (8.4 +/- 1.8%) compared with control levels (1.1 +/- 0.5%; P = 0.03). Additionally, we present preliminary data suggesting that a brief loading regimen is sufficient to rescue osteocytes from this fate. The rapid onset of the observed osteocyte hypoxia, the inhibition of hypoxia by brief loading, and the cellular consequences of oxygen deprivation are suggestive of a novel mechanotransduction pathway with implications across organ systems.  (+info)

Osteocytes are the most abundant cell type in mature bone tissue. They are star-shaped cells that are located inside the mineralized matrix of bones, with their processes extending into small spaces called lacunae and canaliculi. Osteocytes are derived from osteoblasts, which are bone-forming cells that become trapped within the matrix they produce.

Osteocytes play a crucial role in maintaining bone homeostasis by regulating bone remodeling, sensing mechanical stress, and modulating mineralization. They communicate with each other and with osteoblasts and osteoclasts (bone-resorbing cells) through a network of interconnected processes and via the release of signaling molecules. Osteocytes can also respond to changes in their environment, such as hormonal signals or mechanical loading, by altering their gene expression and releasing factors that regulate bone metabolism.

Dysfunction of osteocytes has been implicated in various bone diseases, including osteoporosis, osteogenesis imperfecta, and Paget's disease of bone.

Osteoblasts are specialized bone-forming cells that are derived from mesenchymal stem cells. They play a crucial role in the process of bone formation and remodeling. Osteoblasts synthesize, secrete, and mineralize the organic matrix of bones, which is mainly composed of type I collagen.

These cells have receptors for various hormones and growth factors that regulate their activity, such as parathyroid hormone, vitamin D, and transforming growth factor-beta. When osteoblasts are not actively producing bone matrix, they can become trapped within the matrix they produce, where they differentiate into osteocytes, which are mature bone cells that play a role in maintaining bone structure and responding to mechanical stress.

Abnormalities in osteoblast function can lead to various bone diseases, such as osteoporosis, osteogenesis imperfecta, and Paget's disease of bone.

"Bone" is the hard, dense connective tissue that makes up the skeleton of vertebrate animals. It provides support and protection for the body's internal organs, and serves as a attachment site for muscles, tendons, and ligaments. Bone is composed of cells called osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively, and an extracellular matrix made up of collagen fibers and mineral crystals.

Bones can be classified into two main types: compact bone and spongy bone. Compact bone is dense and hard, and makes up the outer layer of all bones and the shafts of long bones. Spongy bone is less dense and contains large spaces, and makes up the ends of long bones and the interior of flat and irregular bones.

The human body has 206 bones in total. They can be further classified into five categories based on their shape: long bones, short bones, flat bones, irregular bones, and sesamoid bones.

Bone remodeling is the normal and continuous process by which bone tissue is removed from the skeleton (a process called resorption) and new bone tissue is formed (a process called formation). This ongoing cycle allows bones to repair microdamage, adjust their size and shape in response to mechanical stress, and maintain mineral homeostasis. The cells responsible for bone resorption are osteoclasts, while the cells responsible for bone formation are osteoblasts. These two cell types work together to maintain the structural integrity and health of bones throughout an individual's life.

During bone remodeling, the process can be divided into several stages:

1. Activation: The initiation of bone remodeling is triggered by various factors such as microdamage, hormonal changes, or mechanical stress. This leads to the recruitment and activation of osteoclast precursor cells.
2. Resorption: Osteoclasts attach to the bone surface and create a sealed compartment called a resorption lacuna. They then secrete acid and enzymes that dissolve and digest the mineralized matrix, creating pits or cavities on the bone surface. This process helps remove old or damaged bone tissue and releases calcium and phosphate ions into the bloodstream.
3. Reversal: After resorption is complete, the osteoclasts undergo apoptosis (programmed cell death), and mononuclear cells called reversal cells appear on the resorbed surface. These cells prepare the bone surface for the next stage by cleaning up debris and releasing signals that attract osteoblast precursors.
4. Formation: Osteoblasts, derived from mesenchymal stem cells, migrate to the resorbed surface and begin producing a new organic matrix called osteoid. As the osteoid mineralizes, it forms a hard, calcified structure that gradually replaces the resorbed bone tissue. The osteoblasts may become embedded within this newly formed bone as they differentiate into osteocytes, which are mature bone cells responsible for maintaining bone homeostasis and responding to mechanical stress.
5. Mineralization: Over time, the newly formed bone continues to mineralize, becoming stronger and more dense. This process helps maintain the structural integrity of the skeleton and ensures adequate calcium storage.

Throughout this continuous cycle of bone remodeling, hormones, growth factors, and mechanical stress play crucial roles in regulating the balance between resorption and formation. Disruptions to this delicate equilibrium can lead to various bone diseases, such as osteoporosis, where excessive resorption results in weakened bones and increased fracture risk.

Osteogenesis is the process of bone formation or development. It involves the differentiation and maturation of osteoblasts, which are bone-forming cells that synthesize and deposit the organic matrix of bone tissue, composed mainly of type I collagen. This organic matrix later mineralizes to form the inorganic crystalline component of bone, primarily hydroxyapatite.

There are two primary types of osteogenesis: intramembranous and endochondral. Intramembranous osteogenesis occurs directly within connective tissue, where mesenchymal stem cells differentiate into osteoblasts and form bone tissue without an intervening cartilage template. This process is responsible for the formation of flat bones like the skull and clavicles.

Endochondral osteogenesis, on the other hand, involves the initial development of a cartilaginous model or template, which is later replaced by bone tissue. This process forms long bones, such as those in the limbs, and occurs through several stages involving chondrocyte proliferation, hypertrophy, and calcification, followed by invasion of blood vessels and osteoblasts to replace the cartilage with bone tissue.

Abnormalities in osteogenesis can lead to various skeletal disorders and diseases, such as osteogenesis imperfecta (brittle bone disease), achondroplasia (a form of dwarfism), and cleidocranial dysplasia (a disorder affecting skull and collarbone development).

The ulna is one of the two long bones in the forearm, the other being the radius. It runs from the elbow to the wrist and is located on the medial side of the forearm, next to the bone called the humerus in the upper arm. The ulna plays a crucial role in the movement of the forearm and also serves as an attachment site for various muscles.

Physiologic calcification is the normal deposit of calcium salts in body tissues and organs. It is a natural process that occurs as part of the growth and development of the human body, as well as during the repair and remodeling of tissues.

Calcium is an essential mineral that plays a critical role in many bodily functions, including bone formation, muscle contraction, nerve impulse transmission, and blood clotting. In order to maintain proper levels of calcium in the body, excess calcium that is not needed for these functions may be deposited in various tissues as a normal part of the aging process.

Physiologic calcification typically occurs in areas such as the walls of blood vessels, the lungs, and the heart valves. While these calcifications are generally harmless, they can sometimes lead to complications, particularly if they occur in large amounts or in sensitive areas. For example, calcification of the coronary arteries can increase the risk of heart disease, while calcification of the lung tissue can cause respiratory symptoms.

It is important to note that pathologic calcification, on the other hand, refers to the abnormal deposit of calcium salts in tissues and organs, which can be caused by various medical conditions such as chronic kidney disease, hyperparathyroidism, and certain infections. Pathologic calcification is not a normal process and can lead to serious health complications if left untreated.

Mechanical stress, in the context of physiology and medicine, refers to any type of force that is applied to body tissues or organs, which can cause deformation or displacement of those structures. Mechanical stress can be either external, such as forces exerted on the body during physical activity or trauma, or internal, such as the pressure changes that occur within blood vessels or other hollow organs.

Mechanical stress can have a variety of effects on the body, depending on the type, duration, and magnitude of the force applied. For example, prolonged exposure to mechanical stress can lead to tissue damage, inflammation, and chronic pain. Additionally, abnormal or excessive mechanical stress can contribute to the development of various musculoskeletal disorders, such as tendinitis, osteoarthritis, and herniated discs.

In order to mitigate the negative effects of mechanical stress, the body has a number of adaptive responses that help to distribute forces more evenly across tissues and maintain structural integrity. These responses include changes in muscle tone, joint positioning, and connective tissue stiffness, as well as the remodeling of bone and other tissues over time. However, when these adaptive mechanisms are overwhelmed or impaired, mechanical stress can become a significant factor in the development of various pathological conditions.

The Haversian system, also known as the osteon, is the basic unit of structure in compact bone. It was first described by Clopton Havers in 1691. The Haversian system consists of a central canal called the Haversian canal, which contains blood vessels and nerve fibers. Surrounding the Haversian canal are concentric lamellae, which are layers of mineralized matrix. These lamellae are composed of collagen fibrils arranged in a parallel pattern.

Lacunae, or small spaces, are located between the lamellae and contain osteocytes, which are bone cells that help maintain bone health by regulating the exchange of nutrients and waste products between the bone tissue and the bloodstream. Canaliculi, or tiny channels, connect the lacunae to one another and to the Haversian canal, allowing for the movement of fluids and the exchange of nutrients and waste products.

The Haversian system is responsible for the strength and resilience of compact bone. It allows for the distribution of mechanical stresses and strains throughout the bone tissue, helping to prevent fractures. The Haversian systems are interconnected with one another through Volkmann's canals, which are perpendicular to the Haversian canals and allow for the exchange of fluids and nutrients between adjacent Haversian systems.

Cellular mechanotransduction is the process by which cells convert mechanical stimuli into biochemical signals, resulting in changes in cell behavior and function. This complex process involves various molecular components, including transmembrane receptors, ion channels, cytoskeletal proteins, and signaling molecules. Mechanical forces such as tension, compression, or fluid flow can activate these components, leading to alterations in gene expression, protein synthesis, and cell shape or movement. Cellular mechanotransduction plays a crucial role in various physiological processes, including tissue development, homeostasis, and repair, as well as in pathological conditions such as fibrosis and cancer progression.

Bone resorption is the process by which bone tissue is broken down and absorbed into the body. It is a normal part of bone remodeling, in which old or damaged bone tissue is removed and new tissue is formed. However, excessive bone resorption can lead to conditions such as osteoporosis, in which bones become weak and fragile due to a loss of density. This process is carried out by cells called osteoclasts, which break down the bone tissue and release minerals such as calcium into the bloodstream.

Osteoclasts are large, multinucleated cells that are primarily responsible for bone resorption, a process in which they break down and dissolve the mineralized matrix of bones. They are derived from monocyte-macrophage precursor cells of hematopoietic origin and play a crucial role in maintaining bone homeostasis by balancing bone formation and bone resorption.

Osteoclasts adhere to the bone surface and create an isolated microenvironment, called the "resorption lacuna," between their cell membrane and the bone surface. Here, they release hydrogen ions into the lacuna through a process called proton pumping, which lowers the pH and dissolves the mineral component of the bone matrix. Additionally, osteoclasts secrete proteolytic enzymes, such as cathepsin K, that degrade the organic components, like collagen, in the bone matrix.

An imbalance in osteoclast activity can lead to various bone diseases, including osteoporosis and Paget's disease, where excessive bone resorption results in weakened and fragile bones.

Parathyroid Hormone Receptor Type 1 (PTH1R) is a type of G protein-coupled receptor that binds to parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP). It is primarily found in bone and kidney cells.

The activation of PTH1R by PTH or PTHrP leads to a series of intracellular signaling events that regulate calcium homeostasis, bone metabolism, and renal function. In the bone, PTH1R stimulates the release of calcium from bone matrix into the bloodstream, while in the kidney, it increases the reabsorption of calcium in the distal tubule and inhibits phosphate reabsorption.

Mutations in the gene encoding PTH1R can lead to several genetic disorders, such as Blomstrand chondrodysplasia, Jansen metaphyseal chondrodysplasia, and hypoparathyroidism type 1B. These conditions are characterized by abnormalities in bone development, growth, and mineralization.

Bone matrix refers to the non-cellular component of bone that provides structural support and functions as a reservoir for minerals, such as calcium and phosphate. It is made up of organic and inorganic components. The organic component consists mainly of type I collagen fibers, which provide flexibility and tensile strength to the bone. The inorganic component is primarily composed of hydroxyapatite crystals, which give bone its hardness and compressive strength. Bone matrix also contains other proteins, growth factors, and signaling molecules that regulate bone formation, remodeling, and repair.

PHEX (Phosphate Regulating Endopeptidase Homolog, X-Linked) is a gene that encodes for an enzyme called phosphate regulating neutral endopeptidase. This enzyme is primarily expressed in osteoblasts, which are cells responsible for bone formation.

The main function of the PHEX protein is to regulate the levels of a hormone called fibroblast growth factor 23 (FGF23) by breaking it down. FGF23 plays an essential role in maintaining phosphate homeostasis by regulating its reabsorption in the kidneys and its absorption from the gut.

Inactivating mutations in the PHEX gene can lead to X-linked hypophosphatemia (XLH), a genetic disorder characterized by low levels of phosphate in the blood, impaired bone mineralization, and rickets. In XLH, the production of FGF23 is increased due to the lack of regulation by PHEX, leading to excessive excretion of phosphate in the urine and decreased absorption from the gut. This results in hypophosphatemia, impaired bone mineralization, and other skeletal abnormalities.

The tibia, also known as the shin bone, is the larger of the two bones in the lower leg and part of the knee joint. It supports most of the body's weight and is a major insertion point for muscles that flex the foot and bend the leg. The tibia articulates with the femur at the knee joint and with the fibula and talus bone at the ankle joint. Injuries to the tibia, such as fractures, are common in sports and other activities that put stress on the lower leg.

Osteosclerosis is a medical term that refers to an abnormal thickening and increased density of bone tissue. This condition can occur as a result of various diseases or conditions, such as certain types of bone cancer, Paget's disease of bone, fluoride poisoning, or chronic infection of the bone. Osteosclerosis can also be seen in some benign conditions, such as osteopetrosis, which is a rare genetic disorder characterized by an excessively hard and dense skeleton.

In some cases, osteosclerosis may not cause any symptoms and may only be discovered on X-rays or other imaging studies. However, in other cases, it can lead to complications such as bone pain, fractures, or deformities. Treatment for osteosclerosis depends on the underlying cause of the condition and may include medications, surgery, or other therapies.

The skull is the bony structure that encloses and protects the brain, the eyes, and the ears. It is composed of two main parts: the cranium, which contains the brain, and the facial bones. The cranium is made up of several fused flat bones, while the facial bones include the upper jaw (maxilla), lower jaw (mandible), cheekbones, nose bones, and eye sockets (orbits).

The skull also provides attachment points for various muscles that control chewing, moving the head, and facial expressions. Additionally, it contains openings for blood vessels, nerves, and the spinal cord to pass through. The skull's primary function is to protect the delicate and vital structures within it from injury and trauma.

The periosteum is a highly vascularized and innervated tissue that surrounds the outer surface of bones, except at the articular surfaces. It consists of two layers: an outer fibrous layer containing blood vessels, nerves, and fibroblasts; and an inner cellular layer called the cambium or osteogenic layer, which contains progenitor cells capable of bone formation and repair.

The periosteum plays a crucial role in bone growth, remodeling, and healing by providing a source of osteoprogenitor cells and blood supply. It also contributes to the sensation of pain in response to injury or inflammation of the bone. Additionally, the periosteum can respond to mechanical stress by activating bone formation, making it an essential component in orthopedic treatments such as distraction osteogenesis.

Bone development, also known as ossification, is the process by which bone tissue is formed and grows. This complex process involves several different types of cells, including osteoblasts, which produce new bone matrix, and osteoclasts, which break down and resorb existing bone tissue.

There are two main types of bone development: intramembranous and endochondral ossification. Intramembranous ossification occurs when bone tissue forms directly from connective tissue, while endochondral ossification involves the formation of a cartilage model that is later replaced by bone.

During fetal development, most bones develop through endochondral ossification, starting as a cartilage template that is gradually replaced by bone tissue. However, some bones, such as those in the skull and clavicles, develop through intramembranous ossification.

Bone development continues after birth, with new bone tissue being laid down and existing tissue being remodeled throughout life. This ongoing process helps to maintain the strength and integrity of the skeleton, allowing it to adapt to changing mechanical forces and repair any damage that may occur.

"Weight-bearing" is a term used in the medical field to describe the ability of a body part or limb to support the weight or pressure exerted upon it, typically while standing, walking, or performing other physical activities. In a clinical setting, healthcare professionals often use the term "weight-bearing exercise" to refer to physical activities that involve supporting one's own body weight, such as walking, jogging, or climbing stairs. These exercises can help improve bone density, muscle strength, and overall physical function, particularly in individuals with conditions affecting the bones, joints, or muscles.

In addition, "weight-bearing" is also used to describe the positioning of a body part during medical imaging studies, such as X-rays or MRIs. For example, a weight-bearing X-ray of the foot or ankle involves taking an image while the patient stands on the affected limb, allowing healthcare providers to assess any alignment or stability issues that may not be apparent in a non-weight-bearing position.

X-ray microtomography, often referred to as micro-CT, is a non-destructive imaging technique used to visualize and analyze the internal structure of objects with high spatial resolution. It is based on the principles of computed tomography (CT), where multiple X-ray images are acquired at different angles and then reconstructed into cross-sectional slices using specialized software. These slices can be further processed to create 3D visualizations, allowing researchers and clinicians to examine the internal structure and composition of samples in great detail. Micro-CT is widely used in materials science, biology, medicine, and engineering for various applications such as material characterization, bone analysis, and defect inspection.

Extracellular matrix (ECM) proteins are a group of structural and functional molecules that provide support, organization, and regulation to the cells in tissues and organs. The ECM is composed of a complex network of proteins, glycoproteins, and carbohydrates that are secreted by the cells and deposited outside of them.

ECM proteins can be classified into several categories based on their structure and function, including:

1. Collagens: These are the most abundant ECM proteins and provide strength and stability to tissues. They form fibrils that can withstand high tensile forces.
2. Proteoglycans: These are complex molecules made up of a core protein and one or more glycosaminoglycan (GAG) chains. The GAG chains attract water, making proteoglycans important for maintaining tissue hydration and resilience.
3. Elastin: This is an elastic protein that allows tissues to stretch and recoil, such as in the lungs and blood vessels.
4. Fibronectins: These are large glycoproteins that bind to cells and ECM components, providing adhesion, migration, and signaling functions.
5. Laminins: These are large proteins found in basement membranes, which provide structural support for epithelial and endothelial cells.
6. Tenascins: These are large glycoproteins that modulate cell adhesion and migration, and regulate ECM assembly and remodeling.

Together, these ECM proteins create a microenvironment that influences cell behavior, differentiation, and function. Dysregulation of ECM proteins has been implicated in various diseases, including fibrosis, cancer, and degenerative disorders.

Vitallium is not a medical term per se, but rather a trademarked name for a specific alloy that is often used in the medical field, particularly in orthopedic and dental applications. The term "Vitallium" was first coined by the International Nickel Company in 1932 to describe their cobalt-chromium-molybdenum alloy.

Medical Vitallium is typically composed of approximately 60% cobalt, 25% chromium, and 7.5% molybdenum, with trace amounts of other elements like carbon, manganese, silicon, and iron. This specific combination of metals results in an alloy that has several desirable properties for medical applications:

1. High strength-to-weight ratio: Vitallium is exceptionally strong and durable, making it suitable for load-bearing implants such as artificial hip or knee joints.
2. Corrosion resistance: The alloy exhibits excellent corrosion resistance in the human body, which helps to ensure the longevity of medical devices made from it.
3. Biocompatibility: Vitallium has been shown to be biocompatible, meaning that it does not typically cause adverse reactions or rejection when implanted into the human body.
4. Wear resistance: The alloy's hardness and durability make it resistant to wear, which is particularly important in dental applications where components like crowns and bridges must withstand constant use.
5. Magnetic resonance imaging (MRI) compatibility: Vitallium is generally considered safe for use in MRI scans, as it does not interfere significantly with the magnetic field or radiofrequency pulses used during the procedure.

Overall, while "Vitallium" may not be a medical term itself, it represents an important alloy that has contributed significantly to advancements in orthopedic and dental medicine.

REceptor Activator of NF-kB (RANK) Ligand is a type of protein that plays a crucial role in the immune system and bone metabolism. It belongs to the tumor necrosis factor (TNF) superfamily and is primarily produced by osteoblasts, which are cells responsible for bone formation.

RANK Ligand binds to its receptor RANK, which is found on the surface of osteoclasts, a type of cell involved in bone resorption or breakdown. The binding of RANK Ligand to RANK activates signaling pathways that promote the differentiation, activation, and survival of osteoclasts, thereby increasing bone resorption.

Abnormalities in the RANKL-RANK signaling pathway have been implicated in various bone diseases, such as osteoporosis, rheumatoid arthritis, and certain types of cancer that metastasize to bones. Therefore, targeting this pathway with therapeutic agents has emerged as a promising approach for the treatment of these conditions.

Familial Hypophosphatemic Rickets (FHR) is a genetic disorder characterized by impaired reabsorption of phosphate in the kidneys, leading to low levels of phosphate in the blood (hypophosphatemia). This condition results in defective mineralization of bones and teeth, causing rickets in children and osteomalacia in adults.

FHR is typically caused by mutations in the PHEX gene, which encodes a protein that helps regulate phosphate levels in the body. In FHR, the mutation leads to an overproduction of a hormone called fibroblast growth factor 23 (FGF23), which increases phosphate excretion in the urine and decreases the activation of vitamin D, further contributing to hypophosphatemia.

Symptoms of FHR may include bowing of the legs, bone pain, muscle weakness, short stature, dental abnormalities, and skeletal deformities. Treatment typically involves oral phosphate supplements and active forms of vitamin D to correct the hypophosphatemia and improve bone mineralization. Regular monitoring of blood phosphate levels, kidney function, and bone health is essential for effective management of this condition.

Connexin 43 is a protein that forms gap junctions, which are specialized channels that allow for the direct communication and transport of small molecules between adjacent cells. Connexin 43 is widely expressed in many tissues, including the heart, brain, and various types of epithelial and connective tissues. In the heart, connexin 43 plays a crucial role in electrical conduction and coordination of contraction between cardiac muscle cells. Mutations in the gene that encodes connexin 43 have been associated with several human diseases, including certain types of cardiac arrhythmias and skin disorders.

Osteoprotegerin (OPG) is a soluble decoy receptor for the receptor activator of nuclear factor kappa-B ligand (RANKL). It is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in regulating bone metabolism. By binding to RANKL, OPG prevents it from interacting with its signaling receptor RANK on the surface of osteoclast precursor cells, thereby inhibiting osteoclast differentiation, activation, and survival. This results in reduced bone resorption and increased bone mass.

In addition to its role in bone homeostasis, OPG has also been implicated in various physiological and pathological processes, including immune regulation, cancer progression, and cardiovascular disease.

The alveolar process is the curved part of the jawbone (mandible or maxilla) that contains sockets or hollow spaces (alveoli) for the teeth to be embedded. These processes are covered with a specialized mucous membrane called the gingiva, which forms a tight seal around the teeth to help protect the periodontal tissues and maintain oral health.

The alveolar process is composed of both compact and spongy bone tissue. The compact bone forms the outer layer, while the spongy bone is found inside the alveoli and provides support for the teeth. When a tooth is lost or extracted, the alveolar process begins to resorb over time due to the lack of mechanical stimulation from the tooth's chewing forces. This can lead to changes in the shape and size of the jawbone, which may require bone grafting procedures before dental implant placement.

... which may further differentiate to osteocytes). Osteoblasts/osteocytes develop in mesenchyme. In mature bones, osteocytes and ... Osteocytes are also a key endocrine regulator in the metabolism of minerals such as phosphates. Osteocyte-specific proteins ... Osteocyte regulation can be linked to disease. For example, Lynda Bonewald determined that osteocytes make FGF23, which travels ... Osteocytes are an important regulator of bone mass. Osteocytes contain glutamate transporters that produce nerve growth factors ...
Osteocytes are cells, embedded in the mineralized matrix of bone structure, which are important in muscle-bone interactions and ... Bonewald discovered that osteocytes and muscle cells send signals to each other that influence growth and deterioration of both ... She has developed tools which are used globally by researches to study osteocyte biology and function. She holds nine patents. ... It will ruin your career.'" Bonewald went on to make important discoveries relating to astrocytes and osteocytes. Astrocytes ...
Robling AG, Bonewald LF (February 2020). "The Osteocyte: New Insights". Annual Review of Physiology. 82 (1): 485-506. doi: ... Uda, Yuhei; Azab, Ehab; Sun, Ningyuan; Shi, Chao; Pajevic, Paola Divieti (August 2017). "Osteocyte Mechanobiology". Current ... actively synthesizing osteoid containing two osteocytes. Collapse of vertebra on the right, normal on the left Osteoporosis can ...
... osteocytes are also present in bone. Precursors to osteoclasts, called pre-osteoclasts, express surface receptors called RANK ( ...
December 2003). "Osteocyte control of bone formation via sclerostin, a novel BMP antagonist". The EMBO Journal. 22 (23): 6267- ... Sclerostin is produced primarily by the osteocyte but is also expressed in other tissues, and has anti-anabolic effects on bone ... Bellido T, Saini V, Pajevic PD (June 2013). "Effects of PTH on osteocyte function". Bone. 54 (2): 250-7. doi:10.1016/j.bone. ... Sclerostin production by osteocytes is inhibited by parathyroid hormone, mechanical loading, estrogen and cytokines including ...
... whereas apoptotic osteocytes tend to induce osteoclast stimulation. Stimulation of osteocyte apoptosis by alcohol exposure may ... Osteocyte activity plays a key role in this process. Conditions that result in a decrease in bone mass can either be caused by ... Verborgt O, Tatton NA, Majeska RJ, Schaffler MB (May 2002). "Spatial distribution of Bax and Bcl-2 in osteocytes after bone ... Bonewald LF (February 2011). "The amazing osteocyte". Journal of Bone and Mineral Research. 26 (2): 229-238. doi:10.1002/jbmr. ...
Disorganized osteocytes were abundant in the cortex. The outer cortex contains lines of arrested growth, but does not contain ... The dense vasularization, anastomosis in the humerus, and disorganization of osteocytes indicates a growth rate higher than ...
Osteoblasts actively synthesizing osteoid containing two osteocytes. Osteoclast, with bone below it, showing typical ...
Osteocytes remain alive and are connected by cell processes to a surface layer of osteoblasts. Osteocytes have important ... The gap junctions also connect deeper layers of cells to the surface layer (osteocytes when surrounded by bone). This was ... Osteoclasts break down bone tissue, and along with osteoblasts and osteocytes form the structural components of bone. In the ... Feedback from physical activity maintains bone mass, while feedback from osteocytes limits the size of the bone-forming unit. ...
FGF23 is secreted by osteocytes in response to increased calcitriol and phosphate. FGF23 acts on the kidneys by decreasing the ... Robling AG, Bonewald LF (February 2020). "The Osteocyte: New Insights". Annual Review of Physiology. 82 (1): 485-506. doi: ...
Robling, Alexander G.; Bonewald, Lynda F. (10 February 2020). "The Osteocyte: New Insights". Annual Review of Physiology. 82 (1 ... the osteocyte is the major source of RANKL regulating bone remodeling. RANKL derived from other cell types contributes to bone ... "Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling ... "Evidence for osteocyte regulation of bone homeostasis through RANKL expression". Nature Medicine. 17 (10): 1231-1234. doi: ...
Osteocytes are the most abundant cells in the bone and they are responsible for bone health. Osteocytes are important ... June 2021). "Osteocytes regulate neutrophil development through IL-19: a potent cytokine for neutropenia treatment". Blood. 137 ... Metzger CE, Narayanan SA (2019). "The Role of Osteocytes in Inflammatory Bone Loss". Frontiers in Endocrinology. 10: 285. doi: ... or mTORC1 in osteocytes shows a dramatic increase in IL-19 production and expands neutrophil precursor numbers. IL-19 ...
Osteocytes do not entirely fill up the canaliculi. The remaining space is known as the periosteocytic space, which is filled ... Materials picked up by osteocytes adjacent to blood vessels are distributed throughout the bone matrix via the canaliculi. The ... This fluid contains substances too large to be transported through the gap junctions that connect the osteocytes. In cartilage ... The radiating processes of the osteocytes (called filopodia) project into these canals. These cytoplasmic processes are joined ...
The majority of the current data supports the concept that bone mass is controlled by LRP5 through the osteocytes. Mice with ... Zhao L, Shim JW, Dodge TR, Robling AG, Yokota H (May 2013). "Inactivation of Lrp5 in osteocytes reduces young's modulus and ... Burgers TA, Williams BO (Jun 2013). "Regulation of Wnt/β-catenin signaling within and from osteocytes". Bone. 54 (2): 244-9. ... Bone mechanotransduction occurs through Lrp5 and is suppressed if Lrp5 is removed in only osteocytes. There are promising ...
Sclerostin, one of the inhibitors of LRP6, is a promising osteocyte-specific Wnt antagonist in osteoporosis clinical trials. ... Burgers TA, Williams BO (June 2013). "Regulation of Wnt/beta-catenin signaling within and from osteocytes". Bone. 54 (2): 244- ...
Most cells in bones are either osteoblasts, osteoclasts, or osteocytes. Bone tissue is a type of dense connective tissue. One ...
Schweitzer, M.H.; Zheng, W.; Cleland, T.P.; Bern, M. (2013). "Molecular analyses of dinosaur osteocytes support the presence of ...
The cellular component of bone consists of osteoblasts, osteocytes and osteoclasts. Bone is lost through the process of ...
Schweitzer MH, Zheng W, Cleland TP, Bern M (2012-10-17). "Molecular analyses of dinosaur osteocytes support the presence of ...
Osteoblasts are involved in the creation and mineralisation of bone; osteocytes and osteoclasts are involved in the ...
Schweitzer MH, Zheng W, Cleland TP, Bern M (January 2013). "Molecular analyses of dinosaur osteocytes support the presence of ...
Osteocyte lacunae are oval-shaped and randomly distributed. Despite its tiny size, histology supports the idea that the ... Parallel-fibered bone, lines of arrested growth, and flattened osteocyte lacunae are all correlated with the animal having been ...
In histology, a lacuna is a small space, containing an osteocyte in bone, or chondrocyte in cartilage. The lacunae are situated ... Each lacuna is occupied during life by a branched cell, termed an osteocyte, bone-cell or bone-corpuscle. Lacunae are connected ... A lacuna never contains more than one osteocyte. Sinuses are an example of lacuna. The cartilage cells or chondrocytes are ... "Osteocyte lacuna size and shape in women with and without osteoporotic fracture". Journal of Biomechanics. 37 (4): 563-572. doi ...
Civitelli, R (2008). "Cell-cell communication in the osteoblast/osteocyte lineage". Archives of Biochemistry and Biophysics. ...
Osteocyte lacunae are abundant, as with other dinosauromorphs. Some of the longitudinal canals branch into irregular forms (in ...
Of the four major types of bone cells, osteocytes are the most common and also exist in a terminal G0 phase. Osteocytes arise ... While osteocytes also have reduced synthetic activity, they still serve bone functions besides generating structure. Osteocytes ...
... and other osteocytes probably for the purposes of communication. Osteocytes remain in contact with other osteocytes in the bone ... while the osteocyte cell processes occupy channels called canaliculi. The many processes of osteocytes reach out to meet ... Osteoblasts and osteocytes are involved in the formation and mineralisation of bone; osteoclasts are involved in the resorption ... Osteoblasts and osteocytes are derived from osteoprogenitor cells, but osteoclasts are derived from the same cells that ...
Some of the osteoblasts become incorporated within the osteoid to become osteocytes. At this point, the osteoid becomes ... When osteoblasts become trapped in the matrix they secrete, they differentiate into osteocytes. Osteoblasts continue to line up ... mineralized resulting in a nidus consisting of mineralized osteoid that contains osteocytes and is lined by active osteoblasts ...
These cells can differentiate into osteocytes, adipocytes, odontoblast, and chondrocytes in vitro. Recent work has shown the ...
"Excitation of Osteocytes by Mechanical Loading-Induced Bone Fluid Shear Stresses," J. Biomech., 27, 339-360 (1994). Han, Y., ... Cowin, S., Schaffler, M., Weinbaum, S., "Mechanotransduction and Strain Amplification in Osteocyte Cell Processes," PNAS, 101( ...

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