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PubMed2006

Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate.

Coating of orthopaedic implants with extracellular bone matrix components was performed to enhance bone healing. Titanium pins of 0.8mm diameter were coated with type I collagen (Ti/Coll), RGD peptide (Ti/RGD) or type I collagen and chondroitin sulfate (Ti/Coll/CS). Uncoated pins (Ti) served as control. The pins were inserted as intramedullary nails into the tibia of male adult Wistar rats. Six specimens of each group were retrieved at 4, 7, 14 and 28 days. All implants healed uneventfully without adverse reactions. ED 1-positive macrophages appeared in higher numbers around Ti/RGD at day 4 and around Ti at day 14 after implantation (p < 0.05). TRAP-positive osteoclasts and precursors were abundant around Ti/Coll/CS at day 7 (p < 0.05). A significant increase in osteopontin-positive osteoblasts was seen around Ti/Coll/CS implants at days 7 and 14, and around Ti/RGD at day 14 (p < 0.05). At day 28, 62% of Ti, 76% of Ti/Coll, 85%* of Ti/RGD and 89%* of Ti/CoIl/CS (*p < 0.05) implants were covered with newly formed lamellar bone. The addition of extracellular matrix components significantly enhances bone remodelling in the early stages of bone healing around Ti implants, eventually leading to increased new bone formation at the implant surface after 4 weeks.

Animals↗
PubMed2003

Bone graft for revision hip arthroplasty: biology and future applications.

Revision total hip arthroplasty often presents surgeons with difficult bone loss problems. The selection of an appropriate bone graft is influenced by the size of the bone defect, the location, the biology of the bone graft site, and whether the graft is required for structural support. Autogenous bone graft remains the gold standard bone graft material but there only is a limited amount available and there is morbidity associated with the harvesting of these grafts. The most frequently used bone graft materials include autogenous iliac crest bone graft, cancellous allograft chips, demineralized bone matrix, and bulk structural allografts (femoral head, distal or proximal femoral allograft, whole acetabuli, and femoral strut grafts). It often is difficult to determine on plain radiographs whether nonstructural grafts actually incorporate into the host bone. Recently, attention has focused on the use of new materials for bone grafting including: new demineralized bone matrices, ceramics, autologous platelet concentrates, recombinant proteins, and stem cells. The purpose of this review was to assess the biologic potential of these nonstructural grafts in revision hip arthroplasty and their limitations. Are these agents actually incorporating into host bone? Future bone graft options, including tissue engineering and gene therapy will be discussed briefly.

Arthroplasty, Replacement, Hip↗
PubMed1983

Human bone morphogenetic protein (hBMP).

Human bone morphogenetic protein (hBMP) was chemically extracted from demineralized gelatinized cortical bone matrix by means of a CaCl2 X urea inorganic-organic solvent mixture, differential precipitation in guanidine hydrochloride, and preparative gel electrophoresis. hBMP is isolated in quantities of 1 mg/kg of wet weight of fresh bone, and has the amino-acid composition of an acidic polypeptide. The mol wt is 17 to 18 k-Da (kilodaltons). Implants of the isolated 17-kDa protein are very rapidly adsorbed and produce a smaller volume of bone than protein fractions consisting of 24-, 17-, and 14-kDa proteins. Since the isolated 24- and 14-kDA components lack hBMP activity, the kinetics of the bone morphogenetic processes including the function of other proteins as carrier molecules, await investigation.

Adult↗
PubMed1995

Osteoinductive agents. Basic science and clinical applications.

Demineralized bone matrix (DBM) is well characterized as an osteoinductive agent. This article reviews the historical perspectives and current body of knowledge on the mechanisms of induced osteogenesis and the factors contained within DBM, which can induce bone formation. The use of DBM and osteoinductive agents to treat bone defects and nonunions in both animal models and human conditions in orthopedic and reconstructive surgery are discussed.

Animals↗
PubMed1997

Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes.

Matrix vesicles have a critical role in the initiation of mineral deposition in skeletal tissues, but the ways in which they exert this key function remain poorly understood. This issue is made even more intriguing by the fact that matrix vesicles are also present in nonmineralizing tissues. Thus, we tested the novel hypothesis that matrix vesicles produced and released by mineralizing cells are structurally and functionally different from those released by nonmineralizing cells. To test this hypothesis, we made use of cultures of chick embryonic hypertrophic chondrocytes in which mineralization was triggered by treatment with vitamin C and phosphate. Ultrastructural analysis revealed that both control nonmineralizing and vitamin C/phosphatetreated mineralizing chondrocytes produced and released matrix vesicles that exhibited similar round shape, smooth contour, and average size. However, unlike control vesicles, those produced by mineralizing chondrocytes had very strong alkaline phosphatase activity and contained annexin V, a membrane-associated protein known to mediate Ca2+ influx into matrix vesicles. Strikingly, these vesicles also formed numerous apatite-like crystals upon incubation with synthetic cartilage lymph, while control vesicles failed to do so. Northern blot and immunohistochemical analyses showed that the production and release of annexin V-rich matrix vesicles by mineralizing chondrocytes were accompanied by a marked increase in annexin V expression and, interestingly, were followed by increased expression of type I collagen. Studies on embryonic cartilages demonstrated a similar sequence of phenotypic changes during the mineralization process in vivo. Thus, chondrocytes located in the hypertrophic zone of chick embryo tibial growth plate were characterized by strong annexin V expression, and those located at the chondro-osseous mineralizing border exhibited expression of both annexin V and type I collagen. These findings reveal that hypertrophic chondrocytes can qualitatively modulate their production of matrix vesicles and only when induced to initiate mineralization, will release mineralization-competent matrix vesicles rich in annexin V and alkaline phosphatase. The occurrence of type I collagen in concert with cartilage matrix calcification suggests that the protein may facilitate crystal growth after rupture of the matrix vesicle membrane; it may also offer a smooth transition from mineralized type II/type X collagen-rich cartilage matrix to type I collagen-rich bone matrix.

Animals↗
PubMed1991

Gene expression in osteoblastic cells.

Osteoblasts, the bone-forming cells, synthesize the macromolecules of the bone matrix including: type I collagen; osteocalcin; osteonectin; osteopontin; proteoglycan I and II; bone sialoprotein; matrix gla-protein; bone glycoprotein 75; several other proteins, which have not been extensively characterized; growth factors, including transforming growth factor beta and fibroblast growth factor. Osteoblasts also have high levels of the membrane-bound enzyme, alkaline phosphatase, which plays a role in matrix mineralization, and receptors for tissue-specific hormones, such as parathyroid hormone, as well as many other hormones, cytokines and growth factors, which regulate bone growth, differentiation and metabolism. The expression of these various proteins, most of which are not unique to bone but which together characterize the bone phenotype, is induced during osteoblastic differentiation in a stepwise fashion, suggestive of multiple regulatory factors. The detailed sequence of the expression of osteoblastic genes in situ has not been fully characterized. It appears that type I collagen and alkaline phosphatase are expressed early during the commitment to the osteoblastic phenotype, whereas osteopontin and osteocalcin appear late during osteoblastic differentiation. Diversity among "osteoblastic" cells is also apparent, probably not all osteoblastic cells express all the features. A large number of osteoblastic models are currently available to study the expression of osteoblast-related genes in vitro. These include primary cultures from calvaria or trabecular bone from several species, including humans, osteosarcoma-derived cell lines, and experimentally immortalized cells. Some of these in vitro models, especially the calvaria-derived cultures, undergo changes which mimic osteoblastic differentiation in vivo. The study of these and other cell models started providing insights into the regulation of gene expression in osteoblastic cells. In addition to a vast body of information on the conditions required for the expression of various proteins in culture and their regulation by hormones and growth factors, more detailed information on specific genes has recently been obtained. For example, regulation of type I collagen gene expression has been studied in osteosarcoma cell lines where 1,25(OH)2 vitamin D3 was shown to act via specific DNA segment(s) in the 5' flanking region of the gene, while parathyroid hormone affected gene expression by altering the stability of the transcripts. TGF beta 1, which stimulates osteogenesis, was shown to promote the transcription of osteopontin and type I collagen, the latter effect requiring the binding site for the transactivating protein, nuclear factor I.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Effects of sodium acetate on rat bone-nodule formation and mineralization in vitro.

Sodium acetate reportedly promotes bone atrophy by inducing resorption and inhibiting osteoprogenitor-cell proliferation, but little is known about its effects on bone-matrix deposition and mineralization by a population containing osteoprogenitor cells. The objective here was to assess the effects of 1-20 mM sodium acetate on the proliferation and differentiation of these cells and their resultant bone-nodule formation and mineralization in an in vitro assay. Exposure to 10 mM sodium acetate had no effect on cellular proliferation but significantly increased the production and mineralization of bone nodules (p < 0.01), suggesting that it affected osteoprogenitor differentiation and subsequent metabolism. However, 10 mM acetate did not increase net bone mass. Dilutions of 1-5 and 20 mM inhibited cellular proliferation and resultant bone-nodule formation and mineralization, significantly reducing the percentage bone area as compared to controls (p < 0.001). These data suggest that 1-5 and 20 mM sodium acetate significantly inhibit bone deposition, whereas 10 mM has no effects, which could contribute to iatrogenic metabolic bone disease in patients receiving either renal dialysis or total parenteral nutrition.

Analysis of Variance↗
PubMed1995

The bone cell biology of osteogenesis imperfecta.

Osteogenesis Imperfecta (OI) has been defined as a heritable connective tissue disorder with variable severity of clinical expression. OI is a type I collagen based disease. Consequently, much research has focused on identifying specific mutations in the pro-alpha (I) genes. Our interest in OI lies in the metabolism of the non-collagenous proteins (NCPs) of the bone matrix. Although type I collagen is the most abundant protein in bone extracellular matrix, it is the NCPs which bind to, modify and have the potential to regulate that collagen matrix. Our approach has been to determine the levels of the NCPs for both OI and age-matched controls. Most recently, we have utilized an in vitro human osteoblast system to study normal and OI NCP metabolism (Fedarko et al. J. Bone Min. Res. 7, 921-930, 1992). It is our hypothesis that the altered stoichiometry of collagen and NCPs is, in part, responsible for the phenotypic variation of the disease.

Animals↗
PubMed2002

The cryosurgical ablation of bone tissue by means of a new miniature cryoprobe -- evaluation of the probe and adaption of the method to in vitro human bone.

Until now, modern miniature cryoprobes have been used successfully for the local destruction of soft-tissue tumors without damaging adjacent healthy tissue. In this study, the methodology of cryoablation was applied to bone, and the freezing effect as well as the cooling capacity of the probe were examined. Freezing was performed by cooling one or two probes, with a diameter of 3.2 mm, to -180 degrees C with liquid nitrogen. The cooling capacity of the probes was determined under optic and thermic control in a homogenous reference gel (gelatin), followed by an in vitro measurement on human bone. The simultaneous use of 2 probes resulted in a synergistic effect which produced an almost spherical expansion of frozen area in the homogenous gelatin. In vitro freezing of human tibiae produced equivalent freezing temperatures, with one or two probes, in comparison to the homogenous gelatin. An adequate tissue cooling of bone matrix can be achieved through the use of one or more miniature cryoprobes so that after in vivo testing, the use of this probe could possibly become an alternative or supplement to the surgical resection of pathologic bone processes.

Bone Matrix↗
PubMed2004

Osteofibrous dysplasia and adamantinoma: correlation of proto-oncogene product and matrix protein expression.

To investigate the relationship between osteofibrous dysplasia (OFD) and adamantinoma, we analyzed the expression of several proto-oncogene products and extracellular matrix proteins by immunohistochemistry and correlated our results with histological and ultrastructural findings. C-fos and c-jun, but not c-Met, were observed in OFD and in the fibrous and epithelial components of differentiated and classical adamantinomas. Staining for collagen IV, laminin and galectin-3, a laminin binding protein was seen in OFD and around cell nests in adamantinoma. E-, P-, and N-cadherin expression was found in all cases of classical adamantinoma, but not in differentiated adamantinoma or OFD. Osteonectin was detected in both the epithelial and fibrous components of adamantinomas, but osteopontin and osteocalcin were not seen in classical adamantinomas. The results show common expression of a number of oncoproteins and bone matrix proteins in adamantinoma and OFD, some of which are associated with mesenchymal-to-epithelial cell transformation. These findings would be in keeping with the hypothesis that OFD represents a precursor lesion of adamantinoma. Differential expression of a number of bone matrix protein in adamantinoma may also be of diagnostic use in distinguishing these 2 lesions immunohistochemically.

Adolescent↗
PubMed2002

[Experimental fusion of the sheep cervical spine. Part I: Effect of cage design on interbody fusion].

INTRODUCTION: There has been a rapid increase in the use of interbody fusion cages as an adjunct to spondylodesis, although experimental data are lacking. A sheep cervical spine interbody fusion model was used to determine the effect of different cage design parameters (endplate-implant contact area, maximum contiguous pore) on interbody fusion. MATERIAL AND METHOD: IN VITRO EVALUATION: 24 sheep cadaver specimens (C2-C5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive flexibility method using a nonconstrained testing apparatus. Four different groups were examined: (1) control group (intact) ( n=24), (2) autologous tricortical iliac crest bone graft ( n=8), (3) Harms cage ( n=8), and (4) SynCage-C ( n=8). IN VIVO EVALUATION: 24 sheep underwent C3/4 discectomy and fusion: group 1: autologous tricortical iliac crest bone graft ( n=8), group 2: Harms cage filled with autologous cancellous iliac crest bone grafts ( n=8), and group 3: SynCage-C filled with autologous cancellous iliac crest bone grafts ( n=8). Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, disc space height (DSH), height index (HI), intervertebral angle (IVA), and endplate angle (EA) were measured. After 12 weeks the animals were killed and fusion sites were evaluated using biomechanical testing in flexion, extension, axial rotation, and lateral bending. Additionally, histomorphological and histomorphometrical analyses were performed. RESULTS: Over a 12-week period the cage groups showed significantly higher values for DSH, HI, IVA, and EA compared to the bone graft. In vivo stiffness was significantly higher for the tricortical iliac crest bone graft and Harms cage than in vitro stiffness. However, there was no difference between in vitro and in vivo stiffness of the SynCage-C. Histomorphometrical evaluation showed a more progressed bone matrix formation in the Harms cage group than in both other groups. CONCLUSION: The parameter endplate-implant contact area was not able to determine subsidence of cages. In contrast, the maximum contiguous pore of a cage significantly correlates with interbody bone matrix formation inside the cage. Additionally, there was no correlation between in vitro and in vivo stiffness of interbody fusion cages. Therefore, biomechanical in vitro studies are not able to determine in vivo outcome of fusion cages. Animal experimental evaluations of interbody fusion cages are essential prior to clinical use.

Animals↗
PubMed1995

Two distinctive BMP-carriers induce zonal chondrogenesis and membranous ossification, respectively; geometrical factors of matrices for cell-differentiation.

A partially purified BMP preparation was combined with a fibrous glass membrane (FGM) or porous particles of hydroxyapatite (PPHAP), and then implanted subcutaneously into the backs of rats. As a control of these new carriers, a conventional carrier of insoluble bone matrix (IBM) was also used. These new geometrically different solid-state carriers induced tissues in quite different manners. FGM/BMP implants induced cartilage formation within the entire inner area of the membrane accompanied by a small amount of bone formation on the surface of the membrane. In contrast, PPHAP/BMP implants induced only bone within the pores of PPHAP without any detectable cartilage formation. Enzyme-linked immunosorbent assay revealed that the type II collagen content in FGM/BMP was six times higher than that in IBM/BMP, while there was no detectable type II collagen in PPHAP/BMP. The results were explained by the geometric properties of the two distinctive carriers.

Animals↗
PubMed2001

The effects of sustained delivery of growth promoting hormones on the proliferation of MG63 cells in culture.

Bone matrix proteins are being identified in mineralized foci in several different pathological states. Irrespective of how these proteins become localized it is of great interest to further define what endocrine factors are necessary for triggering the release of bone matrix proteins. MG63 cells (Osteosarcoma cell line) were seeded at a density of 1 x 10(5) cells/ml onto two 24 well tissue culture plates. The wells were divided into 8 groups of 6 wells/group. Cells in group 1 were provided with media alone and served as a control. Cells in group II, IV, and VI were supplemented with Insulin Like Growth factor-1 (IGF-1), Testosterone (T), or Growth Hormone (GH), respectively. Cells in groups III, V and VII were supplemented with TCPL capsules containing IGF-1, Test or GH, respectively. Cells in group VIII were incubated with sham TCPL and served as vehicle control. Cells were incubated in the presence or absence of hormones for 24, 48 and 72 hours. At the end of each phase, cell damage, cell morphology, cell number and cellular protein concentrations were determined. The results showed a significant increase in MDA initially in all groups, followed by a drop in MDA levels by the 48-hour phase, and thereafter remaining lower than the control. Results also demonstrated a decrease in total cellular protein following administration of hormones by conventional means. Sustained delivery of the hormones by TCPL resulted in only a slight increase in protein levels. Cell count data showed an initial decrease in all groups, followed by a significant increase in cell number at the end of 48 hours and, finally, reaching control levels at the 72 hour period. Morphological evaluation revealed major structural changes associated with sustained delivery as compared to conventional delivery of hormones. For example, sustained delivery of IGF-1 and T resulted in an increase in mitotic figures, swelling, and aggregate formation. Cluster cellular formation were observed on cells exposed to IGF-1 and T by conventional routes.

Calcium Phosphates↗
PubMed2007

Soft tissue and cellular preservation in vertebrate skeletal elements from the Cretaceous to the present.

Soft tissues and cell-like microstructures derived from skeletal elements of a well-preserved Tyrannosaurus rex (MOR 1125) were represented by four components in fragments of demineralized cortical and/or medullary bone: flexible and fibrous bone matrix; transparent, hollow and pliable blood vessels; intravascular material, including in some cases, structures morphologically reminiscent of vertebrate red blood cells; and osteocytes with intracellular contents and flexible filipodia. The present study attempts to trace the occurrence of these four components in bone from specimens spanning multiple geological time periods and varied depositional environments. At least three of the four components persist in some skeletal elements of specimens dating to the Campanian. Fibrous bone matrix is more altered over time in morphology and less likely to persist than vessels and/or osteocytes. Vessels vary greatly in preservation, even within the same specimen, with some regions retaining pliability and other regions almost crystalline. Osteocytes also vary, with some retaining long filipodia and transparency, while others present with short and stubby filipodia and deeply pigmented nuclei, or are pigmented throughout with no nucleus visible. Alternative hypotheses are considered to explain the origin/source of observed materials. Finally, a two-part mechanism, involving first cross-linking of molecular components and subsequent mineralization, is proposed to explain the surprising presence of still-soft elements in fossil bone. These results suggest that present models of fossilization processes may be incomplete and that soft tissue elements may be more commonly preserved, even in older specimens, than previously thought. Additionally, in many cases, osteocytes with defined nuclei are preserved, and may represent an important source for informative molecular data.

Animals↗
PubMed1987

Sodium fluoride as an initiator of osteogenesis from embryonic mesenchyme in vitro.

Sodium fluoride, which preferentially and rapidly becomes incorporated into bone, is a potent stimulator of bone formation. As such, it has been used to increase total bone mass in patients suffering from osteoporosis. How NaF stimulates bone formation is little understood. Farley et al. (Science 222:330-332, 1983) demonstrated that NaF has a direct effect on proliferation and bone-forming activity of isolated bone cells and of bones exposed to NaF in vitro, that is, NaF stimulates ongoing osteogenesis. In this study, we ask whether NaF can allow preosteogenic embryonic mesenchymal cells to undergo their initial differentiation into osteoblasts and to deposit bone matrix. The mesenchymal cells were from mandibular mesenchyme from embryonic chicks. Mesenchyme from the mandibular arches has to undergo a tissue interaction with mandibular arch epithelium until 4 1/2 days of incubation before osteogenesis can be initiated. Therefore, mandibular arch mesenchyme from younger embryos (3 1/2-4 days), enzymatically freed from its epithelium, was used to provide a source of uninduced preosteogenic cells. Mesenchyme was cultured in the presence or absence of NaF (10(-5) M) in both serum-free and serum-supplemented medium. Osteogenesis was only initiated when NaF was present and only in the presence of serum. Mesenchyme from older embryos that failed to undergo osteogenesis in serum-free medium did form bone in the presence of NaF. It is concluded that preosteogenic embryonic mesenchyme can be stimulated by NaF to differentiate into osteoblasts and to deposit bone matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Bioactive bone cement: comparison of AW-GC filler with hydroxyapatite and beta-TCP fillers on mechanical and biological properties.

Three types of bioactive bone cement (designated AWC, HAC, and TCPC), each consisting of bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin and a bioactive filler of apatite and wollastonite containing glass-ceramic (AW-GC), sintered hydroxyapatite (HA), or beta-tricalcium phosphate (beta-TCP) powder were made in order to evaluate the influence of the bioactive filler on the mechanical and biological properties of bone cement. The proportion of filler added to the cements was 70% w/w. The compressive, bending, and tensile strengths and the fracture toughness of AWC were higher than HAC and TCPC under wet conditions. The cements were evaluated in vivo by packing them into the intramedullary canals of rat tibiae. An affinity index that equalled the length of bone in direct apposition to the cement was calculated for each cement and expressed as a percentage of the total length of the cement surface. Histological examination of rat tibiae up to 8 weeks after implantation revealed that AWC had higher bioactivity than HAC and TCPC. New bone had formed along the AWC surface within 2 weeks, and at 4 weeks newly formed bone surrounded the cement surface almost completely. In HAC- and TCPC-implanted tibiae, immature bone had formed directly toward but not along the cement surface at 2 weeks. Observation of cement-bone interfaces showed that AWC had bonded to the bone via a so-called "Ca-P-rich layer"; the cement-bone interface remained stable, and the width of the CA-P-rich layer became thicker with time. On the other hand, in HAC- and TCPC-implanted tibiae, the cement surface fillers were surrounded by new bone and were absorbed gradually to become bone matrix. The cement-bone interfaces went inside the cement with time. Our results indicate that stronger interstitial bonding between the inorganic filler and the organic matrix resin in AWC lead to higher mechanical properties; results also indicate that the more stable cement-bone interface and higher bioactivity of AWC are due to early and uniform apatite formation on the cement surface.

Animals↗
PubMed2001

Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus).

Native and recombinant human bone morphogenetic/osteogenic proteins (BMPs/ OPs) singly initiate bone induction in vivo. The finding of synchronous but spatially different BMPs/OPs expression during periodontal tissue morphogenesis suggests novel therapeutic approaches using morphogen combinations based on recapitulation of embryonic development. Twelve furcation defects prepared in the first and second mandibular molars of three adult baboons (Papio ursinus) were used to assess whether qualitative histological aspects of periodontal tissue regeneration could be enhanced and tissue morphogenesis modified by combined or single applications of recombinant hOP-1 and hBMP-2. Doses of BMPs/OPs were 100 microg of each protein per 1 g of insoluble collagenous bone matrix as carrier. Approximately 200 mg of carrier matrix was used per furcation defect. Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications. Combined applications of hOP-1 and hBMP-2 did not enhance alveolar bone regeneration or new attachment formation over and above the single applications of the morphogens. The results of this study, which is the first to attempt to address the structure-activity relationship amongst BMP/OP family members, indicate that tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, with hOP-1 inducing substantial cementogenesis. hBMP-2 treated defects, on the other hand, showed limited cementum formation but a temporal enhancement of alveolar bone regeneration and remodelling. The demonstration of therapeutic mosaicism in periodontal regeneration will require extensive testing of ratios and doses of recombinant morphogen combinations for optimal tissue engineering in clinical contexts.

Alveolar Process↗
PubMedDate not supplied

Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse.

Osteopetrosis (op/op) is a new mutation in the mouse that is transmitted as an autosomal recessive linked with variant waddler (Va) on chromosome 12. Compared with normal littermates, young op/op mice have excessive accumulations of bone without marrow cavities, increases in bone matrix formation and concentrations of parafollicular cells of the thyroid, and are hypophosphatemic. Osteoclasts from op/op mice are small, few in number and have an abnormal cytoplasmic distribution of the lysosomal enzyme acid phosphatase. In contrast to the three other mutations that transmit osteopetrosis in mice, the skeletal signs of the disease slowly disappear in op/op animals after bone matrix formation declines about 6 weeks after birth from 145 percent to 20 percent of that in normal siblings. The main skeletal defect in op/op mice appears to be a severe restriction in bone remodeling that is capable of slowly removing the excessive skeletal mass characteristic of the disease only after bone formation has declined to one-fifth that of normal littermates.

Animals↗