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PubMed1993

[Topography of tumoral and pseudotumoral lesions of the proximal femur].

This study of the topographic distribution of tumoral and pseudotumoral lesions of the proximal femur shows that certain lesions have a preferential site, for example osteoid osteoma affects the internal cortex of the neck and diaphysis or the intertrochanteric zone; chondroblastoma occurs in zones of epiphyseal ossification of the head; fibrous dysplasia affects the femoral neck, while sparing the epiphyseal femoral head and trochanters. The island of osteosclerosis is situated, at least partially, in the support fan; so-called physiological cysts are situated on or above the midline of the neck and below the basicapital line. Osteolytic or mixed metastases preferentially involve Ward's triangle in the femoral neck and the intertrochanteric region. The sites of these lesions therefore appears to depend on the bony architecture which, in turn, is dependent on mechanical stresses. However, this purely morphological study fails to demonstrate whether mechanical stresses influence the development of these lesions.

Bone Cysts↗
PubMed1988

A histochemical method for the demonstration of calcifying cartilage.

The demonstration of histochemical characteristics in calcifying cartilage is fraught with methodological difficulties including the distinction of mineralized from unmineralized cartilage and the demonstration of cell detail in relatively hard tissue. This study uses the decalcified bone matrix-induced enchondral (endochondral) ossification system to demonstrate a technique of methylmethacrylate embedding, thin sections, and a combination of histochemical stains that distinguishes mineralized from unmineralized cartilage while preserving excellent cell detail. These techniques are applicable to other areas of enchondral ossification and are exemplified by the staining of growth plates.

Animals↗
PubMed1992

Matrix mineralization in hypertrophic chondrocyte cultures. Beta glycerophosphate increases type X collagen messenger RNA and the specific activity of pp60c-src kinase.

The phenomenon of chondrocyte hypertrophy is accompanied by the expression of type X collagen and the appearance of matrix mineralization. These events are also associated with changes in the phosphorylation of intracellular proteins. In this study the addition of 10 mM beta-glycerophosphate to hypertrophic chondrocytes resulted in stimulation of type X collagen synthesis up to 10 days in culture and an increase in the expression of type X collagen mRNA. This was followed by the onset of mineralization and the appearance of calcium hydroxyapatite. In contrast, the addition of beta-glycerophosphate to non-hypertrophic chondrocytes failed to induce expression of type X collagen or to produce changes in calcium and phosphate. The increased formation of type X collagen and of mineral in hypertrophic chondrocytes was accompanied by changes in the tyrosine kinase pp60c-src. While the level of c-src protein decreased approximately 2.5-fold in hypertrophic chondrocytes after 17 days of beta-glycerophosphate treatment, the specific activity of pp60c-src kinase increased approximately 3-fold in the cells that could be induced to mineralize but remained unchanged in cells that did not exhibit this property. Regulation of kinase activity may be an important event in endochondral ossification.

Animals↗
PubMedDate not supplied

Posttraumatic elbow stiffness: evaluation and management.

Posttraumatic elbow stiffness is a common problem that is often difficult to manage. The goal of treatment is to restore a functional range of elbow motion (> or =30 degrees to 130 degrees ). Nonsurgical treatment includes physical therapy and splinting. If nonsurgical treatment has failed, the type of surgical treatment required depends on the extent of degenerative changes. When degenerative changes are absent or mild, soft-tissue release offers reliable increases in elbow motion. When moderate degenerative changes exist within the joint, debridement arthroplasty of osteophytes and soft tissue has shown some success with increase in joint motion. With advanced degenerative changes, the therapeutic options are more limited. Results from biologic resurfacing arthroplasty are unpredictable, and total elbow arthroplasty should be reserved for the lower-demand elbow in a physiologically older individual.

Algorithms↗
PubMed2005

Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7.

Development of the adult form requires coordinated growth and patterning of multiple traits in response to local gene activity as well as to global endocrine and physiological effectors. An excellent example of such coordination is the skeleton. Skeletal development depends on the differentiation and morphogenesis of multiple cell types to generate elements with distinct forms and functions throughout the body. We show that zebrafish touchtone/nutria mutants exhibit severe growth retardation and gross alterations in skeletal development in addition to embryonic melanophore and touch-response defects. These alterations include accelerated endochondral ossification but delayed intramembranous ossification, as well as skeletal deformities. We show that the touchtone/nutria phenotype results from mutations in trpm7, which encodes a transient receptor potential (TRP) family member that functions as both a cation channel and kinase. We find trpm7 expression in the mesonephric kidney and show that mutants develop kidney stones, indicating renal dysfunction. These results identify a requirement for trpm7 in growth and skeletogenesis and highlight the potential of forward genetic approaches to uncover physiological mechanisms contributing to the development of adult form.

Abnormalities, Multiple↗
PubMed1994

1,25-Dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification.

Target cells for 3H-labeled 1 alpha, 25(OH)2 vitamin D3 [1,25(OH)2D3, vitamin D] and its analog 3H-labeled 22-oxa-1 alpha, 25(OH)2 vitamin D3 (OCT) have been identified during endochondral and intramembranous ossification in developing, undecalcified, unembedded bone, using thaw-mount autoradiography. Two-day-old neonatal rats were injected with [3H]1,25(OH)2D3 or [3H]OCT; after 2 h leg, spine, and head were frozen and sectioned. In the epiphyseal-metaphyseal region specific nuclear concentrations of [3H]1,25(OH)2D3 and [3H]OCT were observed in identical cell populations, being low in cells of the articular and resting zone, intermediate in the proliferating zone, and highest in hypertrophic chondrocytes and in osteoblasts and precursor cells. In the primary spongiosa intertrabecular spaces there were a large number of cells with nuclear labeling--probably osteoblasts and precursor cells. In contrast, in the secondary spongiosa intertrabecular spaces, apparent blood-forming cells were mostly unlabeled. Osteoblasts along bone spicules and compact bone in long bones, vertebrae, and head also showed strong nuclear labeling, as did cells of the periosteum. These data suggest that 1,25(OH)2D3 and OCT regulate development, differentiation, and activities of chondrocytes and osteoblasts, including differentiation of resting chondrocytes into proliferating and hypertrophic chondrocytes that involve "chondroclastic" enlargement of lacunae and "trans-differentiation" of surviving hypertrophic chondrocytes; differentiation of stroma cells into osteoblasts; and in periosteum and other regions of intramembranous ossification differentiation of precursor cells and osteoblasts. Nuclear receptor binding and their selective and hierarchical distribution during cell differentiation appear to correspond to multiple genomic effects toward growth, regeneration and repair. The findings indicate a physiological significance and therapeutic potential of 1,25(OH)2D3 and in particular of its less hypercalcemic analog OCT.

Animals↗
PubMed2003

Perspective. Osteoclastogenesis and growth plate chondrocyte differentiation: emergence of convergence.

A "bone" is really a dynamic and highly interactive complex of many cell and tissue types. In particular, for the majority of skeletal elements to develop and grow, the process of endochondral ossification requires a constantly moving interface between cartilage, invading blood vessels, and bone. A great deal has been learned in recent years about the regulation of chondrocyte proliferation and differentiation by hormones, growth factors, and physiologic stimuli during skeletal development and growth. Likewise, the discovery that colony stimulating factor-1 (CSF-1, or M-CSF) and receptor activator of NF-kappaB ligand (RANKL, a tumor necrosis factor superfamily member also called TRANCE, ODF, OPGL, and TNFSF11) are pivotal in communicating from osteoblasts to osteoclasts has led to deeper insights into bone growth, turnover, and maintenance. Little is known, however, about how these two quite different systems communicate to solve the problem of providing integrated, continuous mechanical support during the dynamic invasion of cartilage by bone that characterizes endochondral bone growth. Evidence has accumulated in recent years that provides insight into the communication between growing bone and cartilage in the form of a subset of osteopetrotic mutations, which share a lack of osteoclasts and an accompanying chondrodysplasia of the growth plate. These mutations thus implicate some of the same gene products in regulating chondrocyte differentiation and bone resorption. We also consider expression studies of some known growth plate regulators, such as parathyroid hormone-related protein (PTHrP) and Indian hedgehog (Ihh), in light of this and propose a model in which the osteoclastogenic factors act also on chondrocytes, but downstream of PTRrP and Ihh in regulating proliferation and differentiation, and after early morphogenic patterns are established.

Animals↗
PubMed1991

Retinoic acid treatment induces type X collagen gene expression in cultured chick chondrocytes.

The vitamin A derivative retinoic acid (RA) is widely thought to be involved in cartilage development, but its precise roles and mechanisms of action in this complex process remain unclear. We have tested the hypothesis that RA is involved in chondrocyte maturation during endochondral ossification and, in particular, is an inducer of maturation-associated traits such as type X collagen and alkaline phosphatase. Immature chondrocytes isolated from the caudal region of Day 19 chick embryo sterna were seeded in secondary monolayer cultures and treated either with a high dose (100 nM) or with physiological doses (10-35 nM) of RA for up to 3 days. We found that after an initial lag of about 24 h, physiological doses of RA indeed induced type X collagen gene expression in the immature cells. This induction was not accompanied by obvious changes in expression of the type II collagen and large aggregating proteoglycan core protein genes. As revealed by immunocytochemistry, 30-35% of the cells in cultures treated with RA for 3 days were engaged in type X collagen production. Interestingly, these cells were relatively similar in size to chondrocytes in which no type X collagen was detected, suggesting that chondrocytes can initiate type X collagen production independent of cell hypertrophy. RA treatment also led to increased alkaline phosphatase activity occurring as early as 24 h after the start of treatment. The data in this study indicate that RA may have a role in endochondral ossification as an inducer/promoter of maturation-associated traits during chondrocyte maturation.

Alkaline Phosphatase↗
PubMed1998

Different behavior of human osteoblast-like cells isolated from normal and heterotopic bone In vitro.

In this study, a characterization of human bone-forming cells responsible for heterotopic ossification was carried out in vitro. The biological and biochemical cell characteristics of the heterotopic osteoblast-like (HOB) cells were compared with those of orthotopic osteoblast-like (OB) cells from normal bone and stromal bone marrow cells believed to contain a subpopulation of osteogenic precursor cells. We found that HOB's from the spongiosa of heterotopic ossification required less time until the beginning of migration and the achievement of confluence in vitro compared with OBs from femoral shaft spongiosa. The fraction of mitotically active cells assessed by a clonogenic assay was higher as well in HOB cells. The in vitro studies of mitogenesis and the efficiency of colony formation of osteogenic cells indicate that with increasing differentiation and relative age they become more dependent on growth factors in the medium, otherwise the morphology of osteoblast-like cells changes and they pass irreversibly into the postmitotic stage of the cell cycle. The activity of the alkaline phosphatase is distinctly higher in the HOB than in the OB cells, HOB cells exhibit a lower level of osteocalcin expression compared with OB cells. No significant difference was found between OB and HOB cells in the amount of procollagen of type I sequestered by the cells. After 30 days, HOB and OB cells formed a mineralized matrix on exposure to 2 mM beta-glycerophosphate. Since HOBs were isolated from heterotopic bone that had developed within 3-6 months after hip surgery, the differences in cellular behavior compared with OBs may be attributed to the relatively young age of HOB cells.

Alkaline Phosphatase↗
PubMed2002

Bone morphogenetic protein 3b expressing reindeer antler.

A cDNA sequence of bone morphogenetic protein 3b (BMP-3b) of reindeer antler was produced with degenerative homology primers in polymerase chain reaction (PCR). An in situ hybridization study of BMP-3b mRNA in 1-month-old antler showed expression in most differentiated cells in the antler center. In addition, the bone-inductive capacity of the reindeer antler matrix was evaluated. Decalcified and powdered antler matrix of different stages of antler maturity was implanted in gelatin capsules under the rat dorsal muscle fascia for two implantation periods: 3 and 8 weeks. Allogenic matrix prepared from rat long bones was used as a positive control implant. Heterotopic ossification was evaluated histomorphometrically and densitometrically. Allogenic bone matrix induced rapid osteogenesis and mineral accumulation. Both endochondral and intramembranous ossification was evident, endochondral ossification being the dominant form. Mineral density in the induced ossicle was 115 +/- 48 mg/cm(3) as early as at 3 weeks and 350 +/- 69 mg/cm(3) at 8 weeks. The proportional areas of von Kossa-stained mineral were 3.67 +/- 2.1% and 11.6 +/- 0.07%, respectively. The antler preparations induced mineralization, but significantly less than the allogenic bone matrix. At 8 weeks, mineral density was significantly lower in the cast antler preparation than in the allogenic implants. The morphology of the mineralized areas of the antler preparations showed no ossification.

Animals↗
PubMed2003

Fetal bony pelvis in the bladder exstrophy complex: normal potential for growth?

OBJECTIVES: To provide the first look at the bony histologic features of fetuses with the exstrophy complex, specifically evaluating the endochondral ossification, stage of development, and microscopic potential for normal growth. METHODS: Three fetuses between 28 and 30 weeks of gestation, one with classic bladder exstrophy, one with cloacal exstrophy, and one control, were obtained from France. The bony pelves were dissected and preserved in formalin, and multiple representative sections were sliced from all pelvic areas: pubis, ischium, ilium, and sacrum. These slices were sequentially processed as slides, stained with hematoxylin-eosin, and evaluated microscopically for histologic changes, developmental stage, and degree of endochondral ossification. RESULTS: All slides from the three specimens showed cartilage analogue with endochondral ossification. Histologically the exstrophy specimens were identical to the control and appeared completely normal; bone development was occurring at an expected rate with the potential for continued normal growth. CONCLUSIONS: These new findings illustrate that fetal bone in the exstrophy complex displays normal microscopic growth patterns and unhindered endochondral ossification at 28 weeks of gestation, well beyond the embryologic period. With no evident microscopic bony defect, the gross bony anomalies in exstrophy should be surgically correctable, leading us to conclude that early reapproximation of the physiologic shape of the pelvis could lead to more normal gross bone growth, decreased shortage of bone, and a more appropriate distribution of the mechanical and developmental forces on a closed, normally functioning pelvic ring.

Abortion, Legal↗
PubMed2005

The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage.

UNLABELLED: AUTHOR: Shen G Objective -This review was compiled to explore the role of type X collagen in growth, development and remodeling of articular cartilage by elucidating the linkage between the synthesis of this protein and the phenotypic changes in chondrogenesis and the onset of endochondral ossification. DESIGN: The current studies closely dedicated to elucidating the role of type X collagen incorporating into chondrogenesis and endochondral ossification of articular cartilage were assessed and analyzed to allow for obtaining the mainstream consensus on the bio-molecular mechanism with which type X collagen functions in articular cartilage. RESULTS: There are spatial and temporal correlations between synthesis of type X collagen and occurrence of endochondral ossification. The expression of type X collagen is confined within hypertrophic condrocytes and precedes the embark of endochondral bone formation. Type X collagen facilitates endochondral ossification by regulating matrix mineralization and compartmentalizing matrix components. CONCLUSION: Type X collagen is a reliable marker for new bone formation in articular cartilage. The future clinical application of this collagen in inducing or mediating endochondral ossification is perceived, e.g. the fracture healing of synovial joints and adaptive remodeling of madibular condyle.

Animals↗
PubMed1993

Nutritional rickets: thoughts about pathogenesis.

The pathogenesis of nutritional rickets is not well-understood. While the etiologies include deficiencies of vitamin D, calcium (Ca) or phosphate (PO4), and perhaps aluminium toxicity, the role these nutrients play in the development of tissue level anomalies characteristic of rachitic cartilage and bone has yet to be defined. Reported alterations in the biochemistry of rachitic bone and cartilaginous matrix which could adversely affect mineralization and endochondral ossification are of questionable significance since the tissues mineralize rapidly when exposed to Ca and PO4 salts in vivo and in vitro. The low Ca and PO4 concentrations of the extracellular fluid (ECF) bathing rachitic cartilage and bone matrix suggest that local mechanisms operate to impair mineralization. In healing rickets, the Ca and PO4 content of these tissue fluids increases in the same time-frame it takes to experimentally remineralize the matrices. However, it is not certain what determines the Ca and PO4 content of the ECF. Cytokines which may play a role in the cellular regulation of Ca and PO4 and maintain processes which contribute to normal patterns of endochondral ossification could provide a mechanism common to the pathogenesis of rickets from a variety of causes.

Animals↗
PubMed1985

A disulfide-bonded short chain collagen synthesized by degenerative and calcifying zones of bovine growth plate cartilage.

Studies of collagen synthesis by specific sections of individual fetal bovine costochondral junction growth plates were conducted and histologically related to the zones from which the sections were derived. Sections were metabolically labeled in organ culture to examine the synthesis of collagen and its precursors. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that Type II collagen was the major species synthesized in all tissue sections; 1 alpha, 2 alpha, 3 alpha collagen chains were synthesized in all growth plate sections and to a small extent in the fetal structural cartilage. A short chain collagen was synthesized predominantly in the zones of degeneration and provisional calcification and accounted for 8-12% of the radioactivity in this section. This short chain collagen has 63-kDa subunits which are converted to 46-kDa species by limited proteolysis with pepsin. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that both the pepsin- and non-pepsin-treated forms of short chain collagen are disulfide-bonded. Digestion with bacterial collagenase showed that the 46-kDa and a major portion of the 63-kDa forms are collagenous. Pulse-chase studies in organ culture did not demonstrate an obvious precursor to the 63-kDa form, and there was no conversion to the 46-kDa after 20 h. Synthesis of short chain collagen appears to be specific to the process of endochondral ossification in the growth plate; its appearance may be critical to this transition process.

Animals↗
PubMedDate not supplied

[Mineralization in the bone of the rabbit mandible after Biositall implantation].

Osteogenic morphological results were assessed at the place of contact of an implant biosital with the lower alveolar jaw-bone in 10 rabbits. Primary mineralization was characterized by the presence of active forming cells and calcified calcospherite structures. Intensive primary mineralization suggests biosital to be a stimulus for ossification (bone formation) promoting favorable interaction tissue implant.

Alveolar Process↗
PubMed1998

The cell and molecular biology of fracture healing.

Fracture healing is a complex physiologic process that involves the coordinated participation of several cell types. By using a reproducible model of experimental fracture healing in the rat, it is possible to elucidate the integrated cellular responses that signal the pathways and the role of the extracellular matrix components in orchestrating the events of fracture healing. Histologic characterization of fracture healing shows that intramembranous ossification occurs under the periosteum within a few days after an injury. Events of endochondral ossification occur adjacent to the fracture site and span a period of up to 28 days. Remodeling of the woven bone formed by intramembranous and endochondral ossification proceeds for several weeks. Spatial and temporal expression of genes for major collagens (Types I and II), minor fibrillar collagens (Types IV and XI), and several extracellular matrix components (osteocalcin, osteonectin, osteopontin, fibronectin and CD44) are detected by in situ hybridization. Immunohistochemical studies show that expression of proliferating cell nuclear antigen is both time and space dependent and differentially expressed in the callus tissues formed by the intramembranous and endochondral processes. Chondrocytes involved in endochondral ossification undergo apoptosis (programmed cell death), and early events in fracture healing may be initiated by the expression of early response genes such as c-fos. Additional characterization and elucidation of fracture healing will lay the foundation for subsequent studies aimed at identifying mechanisms for enhancing skeletal repair.

Animals↗
PubMed1990

Detection of talocalcaneal coalitions by magnification bone scintigraphy.

Fibrocartilaginous talocalcaneal coalitions are very difficult to identify on plain radiography in symptomatic children and adolescents before gross ossification occurs. Computed tomography (CT) has been successful in identifying osseous and some fibro-osseous coalitions. In this series, magnification imaging of the tarsus on bone scintigraphy in the medial-lateral projection correctly identified talocalcaneal coalitions, seven of the nine bars were fibrous or fibro-osseous. Three of the fibrous lesions were equivocal or normal on conventional radiography and CT. Physiologic accumulations of activity in the growing hind foot are also presented from a control pediatric population. Magnification scintigraphy of the hind foot is offered as an adjunct to plain radiography and CT in the diagnosis of elusive nonosseous subtalar bars.

Adolescent↗