• Dong YF, Soung do Y, Schwarz EM, O'Keefe RJ, Drissi H. Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. (umassmed.edu)
  • While hypertrophy of chondrocytes is a physiological process implicated in the longitudinal growth of long bones, hypertrophy-like alterations in chondrocytes play a major role in OA. (biomedcentral.com)
  • At fused stage, early markers for osteoblasts and chondrocytes had been upregulated whereas the osteoblast inhibitor and genes concerned in chon drocyte hypertrophy have been downregulated, success also supported by ISH. (pkc-inhibitors.com)
  • Dele tion of Ihh continues to be proven to disrupt the normal pattern of different zones of chondrocyte differentiation during the development plate, whereas Sox9 accelerate chondrocyte differentiation in proliferating chondrocytes but inhibit hypertrophy. (pkc-inhibitors.com)
  • Hypertrophic chondrocytes, a progeny of terminally differentiated chondrocytes from the proliferative zone, cease further proliferation, undergo hypertrophy in columns parallel to the axis of longitudinal elongation, and initiate the production of factors that trigger mineralization and vessel invasion. (pfmjournal.org)
  • Growth hormone (GH), sex hormone, thyroid hormone, as well as glucocorticoids affect chondrocyte proliferation and hypertrophy. (pfmjournal.org)
  • 2018 ). Although TGF β 1 was con- sidered as a reparative mediator by stimulating chondrocyte proliferation and inhibiting chondrocyte hypertrophy (Varela- Eirin et al. (fdocument.org)
  • 2018 ) or a prolonged exposure to TGF β 1 have been demonstrated to boost chondrocyte hypertrophy (Bakker et al. (fdocument.org)
  • The chondrocyte maturation, hypertrophy and calcification occurs in this zone. (orthofixar.com)
  • While STAT1 controls the cell's multiplication ( proliferation ) pace , the MAPK pathway is a key controller of the chondrocyte differentiation ( hypertrophy ) pace (Figure 2) (1). (treatingachondroplasia.com)
  • These factors also have a role in hypertrophic chondrocyte maturation. (wikipedia.org)
  • Prostaglandin E2 inhibits BMP signaling and delays chondrocyte maturation. (umassmed.edu)
  • The skeletal elements of the limb are formed through a process known as endochondral ossification in which condensations of mesenchymal cells differentiate into cartilage and with maturation are replaced by bone. (silverchair.com)
  • In addition, Atf3 mRNA levels are increased in response to cytochalasin D treatment, an inducer of chondrocyte maturation. (biomedcentral.com)
  • In addition to these key regulators of chondrocyte maturation, numerous other transcription factors have been implicated in this process. (biomedcentral.com)
  • Such development pattern shares an overlapping biological behavior with the growth plate, which is a process of mesenchymal stem cells differentiating into chondrogenic cells and then sequentially into fibrocartilage cells ( Killian, 2022 ). (elifesciences.org)
  • In clonal cultures of chondrocytes isolated from embryoid bodies, additional mesenchymal cell types expressing adipogenic properties were observed, which suggests that the subcultured chondrocytes indeed exhibit a certain differentiation plasticity. (uni-luebeck.de)
  • Vascular buds invade the mesenchymal model, bringing osteoprogenitor cells that differentiate into osteoblasts and form the primary ossification centers at 8 weeks. (orthofixar.com)
  • Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. (nature.com)
  • Accordingly, investigations on cellular therapies have therefore moved to progenitor cell populations such as bone marrow derived mesenchymal stem cells (BMSCs), which have the ability to differentiate into cartilage cells 4 . (nature.com)
  • The Sox9 gene is required for the differentiation of mesenchymal precursor cells to chondrocytes and, together with the related L-Sox5 and Sox6 proteins, controls chondrocyte-specific gene expression [ 4 , 5 ]. (biomedcentral.com)
  • Intramembranous ossification is initiated by local condensation of mesenchymal stem cells that differentiate directly into osteoblasts. (mhmedical.com)
  • Chondrocytes are derived from mesenchymal cells through the process of differentiation during embryogenesis. (researchsquare.com)
  • This study provides evidence for further testing on the molecular mechanism of the disease and also propose proteins as candidate markers of OA chondrocyte phenotype. (biomedcentral.com)
  • At a terminal differentiation stage, cells expressing an osteoblast-like phenotype appeared either by transdifferentiation from hypertrophic chondrocytes or directly from osteoblast precursor cells. (uni-luebeck.de)
  • BMPR1a may mediate the effects of BMPs earlier in the differentiation pathway, especially in the transition from resting to proliferative phenotype, whereas BMPR1b may preferentially mediate the effects of BMPs on hypertrophic differentiation. (heightquest.com)
  • Moreover, hEGFR KI/KI mice display accelerated chondrocyte and osteoblast differentiation, a phenotype that is also present in Egfr -/- mice and has not been previously described. (silverchair.com)
  • The conventional approach utilized to induce dedifferentiation in chondrocytes are comprised of adding dedifferentiating agents or techniques which are often highly expensive, require specific conditions and a long time period to convert the chondrocyte phenotype into fibroblastic cells 8 . (researchsquare.com)
  • Within this scaffold MSCs differentiated into chondrocyte and hypertrophic chondrocyte in the different layers. (universityofgalway.ie)
  • Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. (hindawi.com)
  • MSCs have multilineage differentiation potential, allowing them to differentiate, for example, into chondrocytes and osteoblasts, the key cells from the two tissues that constitute the osteochondral unit. (hindawi.com)
  • In contrast to the cost- and labor-intensive cultivation and propagation of cells such as MSCs or articular chondrocytes, the clinical use of "minimally processed" autologous BMA that can be prepared in the operation room as a single-step procedure appears straightforward. (hindawi.com)
  • Chondrocytes were isolated from articular cartilage of ten patients with primary OA undergoing knee replacement surgery and six normal donors undergoing fracture repair surgery without history of joint disease and no OA clinical manifestations. (biomedcentral.com)
  • So, it is of imminent importance to study the molecular process of chondrocytes differentiation and dedifferentiation in order to discover potential therapies to manipulate the activity to rehabilitate chondrogenic functions and morphology to prevent degeneration of articular joints in various cartilage associated diseases. (researchsquare.com)
  • In this protocol, we utilized 2 weeks old New Zealand rabbits to acquire articular chondrocyte that offers more genetic resemblance to human chondrocyte and can be used to accurately study the molecular mechanism behind cartilage degeneration. (researchsquare.com)
  • Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation. (umassmed.edu)
  • Studies have shown that embryonic stem cells are more mechanosensitive than their differentiated counterparts. (wikipedia.org)
  • Here, we show that embryonic stem cells differentiate into chondrocytes, which progressively develop into hypertrophic and calcifying cells. (uni-luebeck.de)
  • In vitro, tenocyte-like cells extracted from the rotator cuff were able to mineralize in osteogenic cultures, and expressed , , and , which are hypertrophic chondrocytes markers. (iasp-pain.org)
  • Currently, the only FDA-approved cell-based therapy for cartilage defects involves autologous chondrocyte implantation: chondrocytes harvested from low-contact areas are expanded in vitro and then re-injected directly into the damaged site 1 . (nature.com)
  • Here we demonstrate that Atf3 mRNA levels increase during mouse chondrocyte differentiation in vitro and in vivo . (biomedcentral.com)
  • PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling. (umassmed.edu)
  • In the lower RZ, greater BMP signaling may help induce differentiation to proliferative chondrocytes. (heightquest.com)
  • The resting zone, a source of stemlike progenitor cells that restores the reservoir of proliferative chondrocytes, is located farthest from the primary ossification center and assumes responsibility for preserving the architectural integrity of the growth plate [ 4 ]. (pfmjournal.org)
  • The transcription factor Sox9 can be found in multiple sites in the body (pancreas, central nervous system, intestines) and it is also found in all chondrocyte progenitor cells, suggesting that they are important in chondrogenesis. (wikipedia.org)
  • Local factors, including transcription factors such as SRY-box 9 protein (SOX9), Runt-related transcription factor 2 (RUNX2), and bone morphogenetic proteins (BMPs), along with signaling pathways such as the Wnt pathway, play critical roles in chondrocyte proliferation and differentiation. (pfmjournal.org)
  • Runx2 (which may also be known as Cbfa1), and Osx (a zinc finger containing transcription factor) are necessary for osteochondroprogenitor cells to differentiate into the osteoblast cell lineage. (wikipedia.org)
  • Sustained runx2 expression, as located in our studies, is additional related with trans differentia tion of chondrocytes into bone cells. (pkc-inhibitors.com)
  • Our data suggest that transcriptional induction of the Atf3 gene in maturing chondrocytes results in down-regulation of cyclin D1 and cyclin A expression as well as activation of RUNX2-dependent transcription. (biomedcentral.com)
  • In contrast, the Runx2 gene (also known as Cbfa1) is essential for differentiation of osteoblasts, but also promotes hypertrophic chondrocyte differentiation [ 5 , 7 ]. (biomedcentral.com)
  • Coordinated chondrocyte proliferation and differentiation are required for normal endochondral bone growth. (biomedcentral.com)
  • Growth and development of endochondral bones is controlled through the highly coordinated proliferation and differentiation of growth plate chondrocytes [ 1 - 3 ]. (biomedcentral.com)
  • When the growth of stem cells residing in the upper part of the growth plate is activated by receiving growth signals such as growth hormones, the proliferation chondrocytes differentiated from the stem cells divide in the longitudinal direction, and the lower part becomes hypertrophic chondrocytes, gradually into bone tissue, growing the bone become longer and taller. (mopscience.org)
  • In endochondral bone formation, parathyroid hormone-related protein (PTHrP)-expressing RZSCs are the source of growth plate chondrocytes, which give rise to bone-forming osteoblasts as well as bone marrow skeletal stem cells 1 . (nature.com)
  • 21 young (8 weeks of age) and 15 adult (16 weeks of age) C57/BL/6 female mice were used{rodents retain a cartilagenous template post growth plate cessation however if LSJL still involves differentiation of stem cells into chondrocytes then it can still work in human adult mice it'll just be harder as mice already have a cartilagenous matrix to work with. (heightquest.com)
  • In an experimental mouse OA model using a microsurgical technique, MMP-13 levels correlate with the presence of pathological chondrocytes that undergo hypertrophic differentiation in the early stage of OA development [ 11 ] and its over-expression can induce the onset of OA through excessive ECM degradation [ 12 ]. (biomedcentral.com)
  • Here we demonstrate that overexpression of ATF3 in primary mouse chondrocytes results in reduced transcription of both genes, as well as decreased activity of a CRE reporter plasmid. (biomedcentral.com)
  • This review provides an overview of the structural aspects of the growth plate, factors influencing chondrocyte function, and their impact on longitudinal bone growth. (pfmjournal.org)
  • Longitudinal growth occurs in this zone with stacking of chondrocytes (the top cell is the dividing "mother" cell). (orthofixar.com)
  • Rotator Cuff Tenocytes Differentiate into Hypertrophic Chondrocyte-Like Cells to Produce Calcium Deposits in an Alkaline Phosphatase-Dependent Manner. (iasp-pain.org)
  • Calcifications were amorphous areas surrounded by a fibrocartilaginous metaplasia containing hypertrophic chondrocyte-like cells that expressed tissue non-specific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which are two key enzymes of the mineralization process. (iasp-pain.org)
  • We provide evidence that tenocytes have a propensity to differentiate into hypertrophic chondrocyte-like cells to produce TNAP-dependent calcium deposits. (iasp-pain.org)
  • Throughout the producing pathology, the marked border amongst the osteoblast growth zones as well as the chondro cytic areas connected for the arches grew to become much less distinct, as proliferating cells and chondrocytes blended through an intermediate zone. (pkc-inhibitors.com)
  • Our suggestion is for that reason that trans differentiated cells create the ectopic bone. (pkc-inhibitors.com)
  • it had been specu lated if stress worry throughout distraction inhibited last differentiation of chondrocytes and rather trans differen tiated these cells into osteoblastic cells. (pkc-inhibitors.com)
  • Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. (ox.ac.uk)
  • First of all, remedy of cultured insulin creating INS 1E cells with all the reversible ER stress inducer cyclopiazonic acid upregulated genes related to ER pressure when concurrently downregulating genes associated with differentiated cell functions. (atpasesignaling.com)
  • To check this hypothesis, we overexpressed inducible types of HES-1 and MSX-1 proteins in mouse ESCs and examined differentiation into Azlocillin sodium salt NC derivatives, including neural, soft muscle tissue, and chondrocyte-like cells, after activation of the transcription elements. (globaltechbiz.com)
  • Manifestation of Hes1 and Msx1 in Wild-type Sera Cells in Pluripotent Circumstances and after NC Differentiation To investigate the part of and in the differentiation of mESCs into neural crest cells, we utilized the stromal cell-inducing activity of Pre-adipose 6 (PA6) cells for 5 times [17], accompanied by the addition of BMP4, which commits cells to differentiate into NC derivatives [6]. (globaltechbiz.com)
  • Undifferentiated cells secrete cartilaginous matrix and differentiate into chondrocytes. (orthofixar.com)
  • The cells responsible for the bone growth in the growth plates are called chondrocytes (Figure 1) (1). (treatingachondroplasia.com)
  • Chondrocytes are the basic cartilage cells that are critical for joint health. (adam.com)
  • However, in various cartilage degenerative diseases, the chondrocytes transition itself to more flattened fibroblast cells with different morphological, genetical and biochemical characteristics which is characterized as dedifferentiation 4,5 . (researchsquare.com)
  • Chondrocytes have the longest cell cycle in the body (similar to central nervous system and muscle cells). (msdmanuals.com)
  • Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. (ox.ac.uk)
  • We had shown earlier that transcription of the cell cycle genes cyclin D1 and cyclin A in chondrocytes is dependent on CREs. (biomedcentral.com)
  • Site-1 protease is essential to growth plate maintenance and is a critical regulator of chondrocyte hypertrophic differentiation in postnatal mice. (nih.gov)
  • The first tissue-engineered, ear-shaped appendages made from bovine chondrocytes and biocompatible scaffolds by the Vacanti group were prone to deformation when xenografted onto immune-compromised mice, highlighting the lack of long-term stability [ 6 ]. (biomedcentral.com)
  • We performed a quantitative proteomic analysis in osteoarthritic and normal chondrocytes followed by functional analyses to investigate proteome changes and molecular pathways involved in OA pathogenesis. (biomedcentral.com)
  • In this review, we summarized key regulatory factors and signaling pathways involved in chondrocyte functions, to understand how they affect chondrocyte growth and development. (pfmjournal.org)
  • This noninflammatory condition is the result of degenerative changes and progressive loss of cartilage, with resultant hypertrophic changes in surrounding bone. (clinicaladvisor.com)
  • Whereas we have utilized 2-deoxy-D-glucose as a dedifferentiating agent which is relatively cheap and quickly induces dedifferentiation in chondrocytes as compared to other methods 9 . (researchsquare.com)
  • β-catenin of the canonical Wnt signalling pathway plays a role in cell fate determination, as it is critical for osteoblastogenesis, and the differentiation of chondrocytes into osteoblasts. (wikipedia.org)
  • And, we furtherly performed single-cell spatial transcriptomic sequencing on postnatal day 1 mouse enthesis, in order to deconvolute bone-tendon junction (BTJ) chondrocytes onto spatial spots. (elifesciences.org)
  • These processes are regulated by a large number of endocrine, paracrine and autocrine hormones and growth factors that, to a large part, act on chondrocyte cell surface receptors. (biomedcentral.com)
  • As we know, fibroblast growth factor receptor 3 ( FGFR3) helps modulating the chondrocyte cell cycle within the growth plate through two main chemical pathways, one managed by a group of enzymes called MAPK and the other defined by its main enzyme STAT1. (treatingachondroplasia.com)
  • The methods used to induce dedifferentiation in cell models of chondrocytes are often time consuming or require expensive reagents. (researchsquare.com)
  • For this purpose, various cell models are deployed such as chicken, bovine, rat and rabbit, chondrocytes as they are analogues to human chondrocytes 7 . (researchsquare.com)
  • Depending on the different effects, the cellular condensations may differentiate into osteogenic or chondrocytic condensations. (wikipedia.org)
  • Growth, metabolism, and differentiation of chondrocytes, which are the key cellular players in this process, are regulated by systemic hormones, local factors, and cellular signaling pathways. (pfmjournal.org)
  • The regulation of chondrocyte function is mediated by several systemic, local, and cellular signaling pathways. (pfmjournal.org)
  • To explore the molecular switches responsible for this two-step differentiation program, we developed a microdissection method to isolate RNA from the resting (RZ), proliferative (PZ), and hypertrophic zones (HZ) of 7-day-old male rats. (heightquest.com)
  • The molecular mechanism behind the shift of chondrocytes phenotypes is yet to be elucidated. (researchsquare.com)
  • These challenges hinder the scientific community to understand the molecular mechanism behind the transition of chondrocyte phenotypes and expedite the discovery of therapeutic agents for various disease. (researchsquare.com)
  • Farther down the growth plate, even greater BMP signaling may help induce hypertrophic differentiation. (heightquest.com)
  • In the growth plate, we found that BMP-2 and -6 are expressed primarily in the hypertrophic zone at levels similar to or greater than those found in the trabecular bone of the metaphysis. (heightquest.com)
  • The growth plate can be stratified into three distinct zones based on the size, morphology, orientation, proliferative potential, and function of chondrocytes: resting, proliferative, and hypertrophic zone. (pfmjournal.org)
  • In this review, we highlight the main MMP-13-related changes in OA chondrocytes, including alterations in the activity and expression level of MMP-13 by upstream regulatory factors, DNA methylation, various non-coding RNAs (ncRNAs), and autophagy. (biomedcentral.com)
  • Providers must be familiar with the clinical and laboratory features that differentiate each type ( Table 1 ) and how they are managed. (clinicaladvisor.com)