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At least 289 records · Page 16Linked to original sources
PubMed1995

Differentiation and mineralization in chick chondrocytes maintained in a high cell density culture: a model for endochondral ossification.

Chondrocytes isolated from the proliferative and differentiating zones of 3-wk-old chick growth plates were cultured in the presence of 10% fetal bovine serum (FBS) and ascorbic acid for up to 21 d in a high cell density culture within Eppendorf tubes. The proliferative, differentiating, and calcification properties of the chondrocytes were examined by immunolocalization and by enzyme histochemical and biochemical methods. The cells maintained a chondrocyte phenotype throughout culture: they were round in shape and synthesized both collagen type II and proteoglycans. The expression of a hypertrophic phenotype was evident by Day 3 of culture and from this time onwards characteristics of terminal differentiation were observed. The cells were positive for both alkaline phosphatase (ALP) activity and c-myc protein and the surrounding matrix stained strongly for collagen type X. Small foci of mineralization associated with individual chondrocytes were first evident by Day 6 and more widespread areas of mineralization occupying large areas of matrix were present by Day 15. Mineralization occurred without the addition of exogenous phosphate to the medium. This culture system displays characteristics that are similar in both morphological and developmental terms to that of chick chondrocyte differentiation and calcification in vivo and therefore offers an excellent in vitro model for endochondral ossification.

Alkaline Phosphatase↗
PubMedDate not supplied

Soft tissue mineralization: roentgen analysis.

Numerous, incompletely understood, and undetermined physiologic factors may exert further but unappreciated influences on the development of ectopic calcification and ossification. In the former instance, in addition to serum calcium and phosphorous ion concentrations, tissue pH, blood supply, hormones, i.e., vitamin D, vitamin A, and various enzymes (e.g., alkaline phosphatase and pyrophosphatase) may all play significant, ancillary, time-dependent, but as yet undetermined roles. Ossification, like calcification, may occur in association with many types of disorders and under a variety of circumstances, some of which, such as trauma, have been reduplicated in the laboratory. However, experimental conditions that produce ectopic bone, as well as the species that are predilected do not always coincide with clinical observations in man. Not only are there differences between species in regard to susceptibility to ectopic bone production under particular circumstances, i.e., rabbits are the most susceptible and mice the least to mechanical injury, but there are differences between individuals. Individual variability in susceptibility to soft tissue ossification suggests either a personal or familial predilection. If such liability is inherited, this would be an example of an ecogenetic condition, in which someone is susceptible to an environmental agent by virtue of genetic constitution. Histocompatibility (HLS) antigens have provided substantiation of this concept. In the case of soft tissue ossification, causative environmental agents could include trauma, burns, hip replacement, and immobility secondary to neurological insults. In the case of soft tissue calcification, trauma, infections, or repeated injections could constitute the triggering environmental event. Not only do individuals at risk develop bone, but those that do tend to do so in characteristic places. Therefore, there is an additional differential susceptibility at various sites in the same individual. In cases with neurological conditions, thigh muscles are more susceptible than paraspinal muscles. The underlying condition is a further moderator, i.e., in paraplegics, thigh muscles are most apt to be involved. Elbows are most commonly affected after burns regardless of the site of the burn. Ectopic ossification also has a further predilection for distribution. Not only are muscle groups unequal in risk in terms of site, but the type of muscle affected is relevant, since skeletal muscles are involved in these same conditions to the exclusion of smooth muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1975

[A clinical observation as example and proof of functional adaptation of bone through longitudinal growth].

The history of the case and findings and follow-up in radiographs when submitted to analysis of the mechanical forces, are an example and proof for : 1. the fact that, in compression forces overlayed by flexion forces, the tension on the pressure aspect of flexion is always larger than on the extension side, since on the flexion side it is the sun of, on the extension side the difference between, the two tensions which are active. 2. Ossification and bone absorption are steered by the amount of tension and will be the greater, the more the tensions exceed or fall short of the "required" tensions which maintain the balance between ossification and bone absorption during the continuous restructuring of bone. 3. In epiphyseal cartilage which physiologically is purely subject to pressure, longitudinal growth will increase when flexion forces overlay on the pressure side where tensions are greatest. This will automatically exclude the overlaying flexion forces.

Adaptation, Physiological↗
PubMed2005

Colchicine inhibits heterotopic ossification: experimental study in rabbits.

BACKGROUND: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain trauma. OBJECTIVES: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization. METHODS: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3-3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/ day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group)--1 week preceding bone marrow injection; group B--on day of injection; and group C--control group. RESULTS: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls where large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification. CONCLUSIONS: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

Animals↗
PubMed1998

Post-traumatic hormonal disturbances: prolactin as a link between head injury and enhanced osteogenesis.

Traumatic brain injury (TBI) combined with fractures of long bones or large joints is often associated with enhanced osteogenesis (early fracture healing accompanied by hypertrophic callus formation and/or heterotopic ossifications). Humoral factors that cause enhanced osteogenesis in patients with TBI are not yet identified. The aim of this study was to reveal if post-traumatic change(s) of hormone levels in patients with TBI and bone fractures could be associated with the phenomenon of enhanced osteogenesis. The blood values of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), parathyroid hormone (PTH) and prolactin (PRL) were studied weekly over a period of three months after injury in patients with bone fractures only, those with TBI only or combined bone fractures and TBI (patients exerting enhanced osteogenesis). Stress-hormones, ACTH and cortisol, or the hormones related to the bone growth (GH and PTH) did not show any particular post-traumatic changes in the blood of patients with combined injury that could be associated with the enhanced osteogenesis. On the other hand, patients with combined bone fractures and TBI accompanied by enhanced osteogenesis had significantly elevated PRL levels in blood during the 5th week of the post-traumatic period. Thus, the maximal PRL values were measured at the time when in this group of patients fractures were in consolidation and hypertrophic callus or heterotopic ossifications were developing (as verified by x-ray imaging). Hence, PRL does not only influence physiology of the bone metabolism but also seems to be one of the humoral factors involved in the phenomenon of enhanced osteogenesis in patients with TBI.

Adrenocorticotropic Hormone↗
PubMed1996

Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II.

Cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinases (cGKs) mediate cellular signaling induced by nitric oxide and cGMP. Mice deficient in the type II cGK were resistant to Escherichia coli STa, an enterotoxin that stimulates cGMP accumulation and intestinal fluid secretion. The cGKII-deficient mice also developed dwarfism that was caused by a severe defect in endochondral ossification at the growth plates. These results indicate that cGKII plays a central role in diverse physiological processes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1974

Relationship of unkeratinized skin to bovine fetal mummification: an hypothesis.

Evidence is reviewed in support of the hypothesis that immature unkeratinized fetal skin must be present if bovine fetal mummification is to occur. The reduction in fetal and amniotic fluid is considered to be the result of intrafetal (fetal death) or prefetal (caruncular damage) effects on the normal net fluid flow from the maternal circulation through the fetal circulation and then across the fetal skin into the amniotic cavity. As the skin is keratinized permeability is reduced drastically thus limiting fluid loss from the fetus.

Amniotic Fluid↗
PubMed1996

Characteristics and mechanism of the ossification of posterior longitudinal ligament in the tip-toe walking Yoshimura (twy) mouse.

To elucidate the mechanism of ossification of the posterior longitudinal ligament (OPLL), we examined the serial changes in the intervertebral disc of tip-toe walking Yoshimura (twy) mouse. At the age of 6 weeks, the volume of the nucleus pulposus increased in all intervertebral discs causing anterior and posterior herniation. Secondary to this herniation, the cartilagineous tissue of the annulus fibrosus was disrupted and showed regenerative proliferation with PCNA-positive cartilagineous cells. These cells were S-100 positive and the matrix was positive for chondroitin-4-sulfate proteoglycan, indicating the development of calcification. At the age of 15 weeks, the regenerative cartilagineous tissue of the annulus fibrosus reached the posterior longitudinal ligament together with neovascularization and appearance of PCNA-positive proliferating primitive mesenchymal cells. These cells were considered to be osteoblasts since they were positive for alkaline phosphatase and the matrix contained type I collagen. Using electron microscopic X-ray analysis, vesicles present in the matrix of regenerative cartilagineous cells of the annulus fibrosus were confirmed to contain calcium phosphate crystals, also indicating the development of calcification. In conclusion, our serial analysis indicates that ossification of posterior longitudinal ligament in twy mouse was triggered by enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilagineous tissues. Enchondral ossification of the new annulus fibrosus cartilagineous cells and membraneous ossification by primitive osteoblasts proceed to the final ossification of the posterior longitudinal ligaments.

Alkaline Phosphatase↗
PubMed2006

T-cell cytokine induction of BMP-2 regulates human mesenchymal stromal cell differentiation and mineralization.

How T-cells, attracted to local sites of inflammation in arthritides, affect heterotopic ossification is presently unknown. Here, we tested the hypothesis that T-cell cytokines play a role in the differentiation of human mesenchymal stromal cells (HMSC) into the osteoblast phenotype by inducing autologous BMP-2, providing a possible mechanism for heterotopic ossification. HMSC from multiple donor bones were treated with either activated T-cell conditioned medium (ACTTCM) or physiological concentrations of the major inflammatory cytokines, TNF-alpha, TGF-beta, IFN-gamma, and IL-17 (TTII), individually or in combinations. ACTTCM induced BMP-2 protein in a time-dependent manner over a 48 h period and alkaline phosphatase (AlkP) within 7 days. In combination, TTII, like ACTTCM, induced AlkP and synergistically induced BMP-2 protein. Either individually, or in combinations of up to three, the T-cell cytokines failed to induce BMP-2 above control levels while a combination of all four cytokines synergistically induced BMP-2 10-fold as assessed by ELISA. TTII induced mineralized matrix as effectively as dexamethasone. Inhibition of p38 MAPK completely inhibited TTII-induced BMP-2 production and matrix mineralization. Real time RT-PCR analysis demonstrated a striking early (within 4 h) increase in BMP-2 gene expression by TTII, which was suppressed by p38 MAP kinase inhibition. In localized chronic inflammatory diseases, T-cell cytokines released at localized sites of inflammation may be the driving force for differentiation of local mesenchymal stromal cells into the osteoblast phenotype thereby playing a significant role in the heterotopic ossification observed in these diseases.

Arthritis↗