The development and structure of the chimpanzee mandible. (1/1613)

The sites of growth and remodeling, and the associated changes in cortical bone structure, have been studied in the chimpanzee mandible and compared with those previously reported in the human and macaque mandibles. The location of the principal sites of growth, and the distribution of the areas of deposition and resorption in the ramus, were found to be similar in all three species. In the chimpanzee, unlike Man, the bone being deposited at the condyle, posterior border of the ramus and coronoid process was plexiform in nature, indicating very rapid growth. The pattern of remodeling in the mandibular body, on the other hand, showed marked species differences at the chin and on the submandibular lingual surface, which account for the contrasts seen in the adult morphology of these regions. Although the pattern of distribution of cortical densities differed from that of surface remodeling, the information they give is complementary in analysing bone growth. The densest regions were found to coincide with sites of consistent lamellar deposition, while the least dense regions were those where plexiform bone was formed. Areas where remodeling led to the greatest reorientation of bone tissue within the cortex showed the greatest disparity between the two patterns.  (+info)

Expression of the paired-box genes Pax-1 and Pax-9 in limb skeleton development. (2/1613)

Vertebrate Pax genes encode a family of transcription factors that play important roles in embryonic patterning and morphogenesis. Two closely related Pax genes, Pax-1 and Pax-9, are associated with early axial and limb skeleton development. To investigate the role of these genes in cartilage formation we have examined the expression profiles of Pax-1 and Pax-9 in developing chick limb mesenchyme in vivo and in vitro. Both transcripts are detected by reverse transcription polymerase chain reaction and Northern blotting throughout chick limb development, from the early bud stages (Hamburger-Hamilton 20-23) to fully patterned appendages (stage 30). Whole-mount in situ hybridization reveals complex, nonoverlapping expression domains of these two genes. Pax-1 transcripts first appear at the anterior proximal margin of the limb buds, while Pax-9 is expressed more distally at what will be the junction of the autopod and the zeugopod. In situ hybridization to serial sections of the girdles reveals that in the pectoral region Pax-1 is expressed proximally in condensed mesenchyme surrounding the junction of the developing scapula, humerus, and coracoid. In the pelvis, Pax-1 is expressed between the femur and the developing acetabulum and along the ventral edge of the ischium; this transcript was also found in the distal hindlimb along the posterior edge of the fibula. Pax-9 transcripts were not detected in the pectoral girdle at any stage, and only weakly in the pelvis along the ventral ischial margin. In the distal parts of both wings and legs, however, Pax-9 is strongly expressed between the anterior embryonic cartilages (e.g., distal radius or tibia) and the anterior ectodermal ridge. The expression of both genes was strongest in undifferentiated cells of precartilage condensations or at the margins of differentiated cartilages, and was absent from cartilage itself. In micromass cultures of chondrifying limb bud mesenchyme expression of Pax-1 and Pax-9 is maintained for up to 3 days in vitro, most strongly at the end of the culture period during chondrogenic differentiation. As seen in vivo, transcripts are found in loose mesenchyme cells at the outer margins of developing cartilage nodules, and are absent from differentiated chondrocytes at the nodule center. Taken together, these investigations extend previous studies of Pax-1 and Pax-9 expression in embryonic limb development while validating limb bud mesenchyme culture as an accessible experimental system for the study of Pax gene function and regulation. Our in vivo and in vitro observations are discussed with reference to 1) the relationship between somitic and limb expression of these two Pax genes, 2) what regulates this expression in different regions of the embryo, and 3) the putative cellular functions of Pax-1 and Pax-9 in embryonic skeletogenesis.  (+info)

An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (3/1613)

Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin-/- mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease.  (+info)

Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital hydrocephalus (ch/Mf1) arise from a winged helix/forkhead transcriptionfactor gene. (4/1613)

Congenital hydrocephalus is an etiologically diverse, poorly understood, but relatively common birth defect. Most human cases are sporadic with familial forms showing considerable phenotypic and etiologic heterogeneity. We have studied the autosomal recessive mouse mutation congenital hydrocephalus ( ch ) to identify candidate human hydrocephalus genes and their modifiers. ch mice have a congenital, lethal hydrocephalus in association with multiple developmental defects, notably skeletal defects, in tissues derived from the cephalic neural crest. We utilized positional cloning methods to map ch in the vicinity of D13Mit294 and confirm that the ch phenotype is caused by homozygosity for a nonsense mutation in a gene encoding a winged helix/forkhead transcription factor ( Mf1 ). Based on linked genetic markers, we performed detailed phenotypic characterization of mutant homozygotes and heterozygotes to demonstrate the pleiotropic effects of the mutant gene. Surprisingly, ch heterozygotes have the glaucoma-related distinct phenotype of multiple anterior segment defects resembling Axenfeld-Rieger anomaly. We also localized a second member of this gene family ( Hfh1 ), a candidate for other developmental defects, approximately 470 kb proximal to Mf1.  (+info)

Growth factors in bone. (5/1613)

Bone contains several growth factors, including bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-beta), insulin-like growth factors I and II (IGF-I and IGF-II), platelet derived growth factor (PDGF) and basic and acidic fibroblast growth factor (bFGF and aFGF). Spatial and temporal variations in the expression and secretion of the various growth factors have been demonstrated in osteoblastic cultures and in various experimental and clinical in vivo models, including fracture healing in humans. Local application of various growth factors influences proliferation, differentiation and protein synthesis in osteoblastic cultures and bone formation in different animal models, including experimental fractures and skeletal defects. The BMPs are the only growth factors known to provoke bone formation heterotopically by making undifferentiated mesenchymal cells differentiate into osteoblasts (osteoinduction). BMPs and other growth factors, soon to become commercially available for clinical use, need a delivery system for their sustained release, as the factors are otherwise rapidly absorbed. Some existing systems inhibit bone formation by inducing chronic inflammation or physically by unresorbed carrier obstructing bone formation. New delivery systems are being investigated.  (+info)

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. (6/1613)

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.  (+info)

Retardation of bone growth in triamcinolone-treated mice. (7/1613)

Immature mice were treated for up to 8 weeks with daily doses of triamcinolone diacetate. The epiphyseal cartilage plate and its surrounding bone from the humeral head were studied histologically at regular intervals. Concomitantly, roentgenographic measurements were performed on the humeri in toto. By the tenth injection significant morphological changes were noted in the cartilaginous plate, followed by complete cessation of bone growth. Severe triglyceride accumulation appeared in the experimental livers and humeral bone marrow. Osteoporosis also occurred and became severe from the fifth week of triamcinolone administration. Possible explanations for the above findings are discussed.  (+info)

Quantitative histology of the human growth plate. (8/1613)

This paper describes a study in the human femur of the relationship between cell division in growth cartilage and overall bone growth. Growth rates for the distal femur from birth to eighteen years were determined from serial radiographs available from the Harpenden Growth Study; An average of 1-4 cm/year was found for the ages of five to eight years. The development of the growth plate is illustrated in a series of photomicrographs of femur sections. These sections were also used for quantitative histology; The length of the proliferation zone was estimated from cell counts to be twenty-four cells per column. On the basis of this value and the measured growth rate, an approximate mean cycle time of twenty days was found for the proliferating cells of the human growth plate. Since the corresponding cycle time is two days for rodent growth plates, which also have a different structure, it is unwise to extrapolate the findings in this tissue from mouse to man.  (+info)