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Results for “Bone Morphogenetic Protein 3”

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At least 19 recordsLinked to original sources
PubMed2001

[Experimental study of in osteogenesis in duced by NIH-3T3 cells transfected with bone morphogenetic protein 3 gene].

OBJECTIVE: To investigate the gene expression, protein synthesis and inducing osteogenetic capacity of NIH-3T3 cells transfected with recombinant human bone morphogenetic protein 3 (rhBMP3) gene. METHODS: Gene recombination technique was used to clone the BMP3 cDNA into PcDNA3 vector directly, and to form a recombined BMP3-PcDNA3 cDNA, which was introduced into NIH-3T3 cells by means of lipofectamine transfer. The total RNA of transfected NIH-3T3 cells was then extracted to verify the mRNA expression of BMP3 using Northern blot method. BMP3 protein synthesis and AKP activity in the transfected cells was checked. Then, the NIH-3T3 cells transfected with BMP3 gene were injected into nude mouse muscle to evaluate the inducing osteogenesis in the muscle. RESULTS: BMP3 gene had been inserted into PcDNA3 vector successfully. There was BMP3 mRNA expression in the total RNA of NIH-3T3 cells with the peak level appearing in the 6th week after transfection, and BMP3 protein was found in NIH-3T3 cells, and the AKP level is much higher in the transfected NIH-3T3 cells than in non-transfected NIH-3T3 cells. Histologic examination revealed that there were a large number of chondrocytes and trabeculae seen in the nude mouse muscle 4 weeks after injection of the transfected NIH-3T3 cells. CONCLUSION: BMP3 is a protein that possesses osteogenetic effect. After transfection with BMP3-PCDNA3, BMP3 mRNA expression and protein formation can be found in NIH-3T3 cells, and the transfected NIH-3T3 cells have the effect of inducing osteogenesis in vivo.

3T3 Cells↗
PubMed2005

Bone morphogenetic protein 3 expression pattern in rat condylar cartilage, femoral cartilage and mandibular fracture callus.

Mandibular condylar cartilage differs from primary cartilage in morphological organization of the chondrocytes and in responses to biomechanical stress and humoral factors. For the first time, we describe the expression of Bmp3 mRNA in relation to types I, II and X collagen mRNA (as determined by in situ hybridization) in chondrocytes of the rat mandibular condylar cartilage, femoral articular cartilage, femoral growth plate cartilage, and temporal cartilage, which transiently appeared in the reparative response stage of mandibular ramus fracture healing. In all cartilages evaluated, Bmp3 was expressed in proliferating chondrocytes that expressed type I collagen in condylar cartilage, articular cartilage, and temporal cartilage appearing during fracture healing. Bmp3 was also found in hypertrophic chondrocytes that expressed type X collagen mRNA in all cartilages evaluated. Furthermore, in remodeling bone, Bmp3 mRNA was strongly expressed in active osteoblast cells in periosteal reaction layers formed after fracture. These findings suggest that Bmp3 expression in a special layer of typical articular cartilage may be regulated by mechanical stress stimulation. We also found that Bmp3 was expressed in the periosteal layers of the bone segments near the fracture site during fracture healing.

Animals↗
PubMed1995

Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells.

We have examined expression of bone morphogenetic protein 3 (BMP-3) mRNA in normal rat osteoblasts in culture as they undergo differentiation to form bone-like structures, and have found that expression of BMP-3 mRNA in primary fetal rat calvarial (FRC) cells is discontinuous and shows at least four different-sized transcripts. BMP-3 mRNA expression has a distinct temporal pattern during bone cell differentiation of FRC osteoblasts. Previously, we showed that BMP-3 mRNA is expressed in normal and neoplastic rat and human prostate tissues, and in human osteosarcoma cells, as multiple transcripts. To compare the nature of these transcripts in different tissues, three cDNA clones encoding BMP-3 have been isolated by reverse transcription-polymerase chain reaction (RT-PCR) and cDNA library screening from human prostate cancer PC-3 cells, rat prostate adenocarcinoma PA III cells, and primary FRC cells. Analysis of these clones has revealed that the nucleotide sequence of BMP-3 found in human prostate cells is identical to that found in human bone cells. The rat BMP-3 sequences from bone and prostate cells are also identical but show a high degree of variation in the pro- or precursor region compared with human BMP-3. The biological significance of these differences in these two species is unknown.

Adenocarcinoma↗
PubMed2002

Collagen-targeted BMP3 fusion proteins arrayed on collagen matrices or porous ceramics impregnated with Type I collagen enhance osteogenesis in a rat cranial defect model.

Bone morphogenetic protein 3 (BMP3) is a potent osteoinductive growth factor belonging to the TGF-beta superfamily. In this study, we engineered a recombinant BMP3 protein to include an auxiliary collagen-targeting domain derived from von Willebrand coagulation factor (vWF). The collagen-targeted BMP3 fusion protein (rhBMP3-C) was expressed in E. coli, purified from bacterial inclusion bodies, renatured under controlled redox conditions, and assayed for biological activity in vitro and in vivo. The renatured rhBMP3-C fusion protein bound tightly to collagen matrices and inhibited DNA synthesis in normal rat calvaria cells and in two out of three human osteosarcoma cell lines tested. Alkaline phosphatase activity was increased in rat calvarial cells and was decreased in osteosarcoma cells in vitro in a dose-dependent manner. Collagen sponges impregnated with rhBMP3-C and implanted subcutaneously in Fischer-344 rats induced dose-dependent dystrophic calcification of the collagen matrix, with no evidence of ectopic bone formation. However, local injection of rhBMP3-C infused in a collagen suspension induced new bone formation on the periosteal surface of rat calvaria. Finally, in a rat cranial defect model, surgical implantation of rhBMP3-C arrayed on either collagen sponges or on porous ceramics coated with Type I collagen exhibited marked osteoinductive properties. Taken together, these results demonstrate the feasibility of engineering and manufacturing targeted-BMPs which exhibit an integral gain-of-function that may be exploited to therapeutic advantage in (i) the enhancement of effective local concentrations, (ii) the prevention of systemic biodistribution and side effects, and (iii) the design of improved osteoinductive matrices.

Alkaline Phosphatase↗
PubMed2003

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis in rabbits.

PURPOSE: We examined the expression pattern of bone morphogenetic proteins (BMPs) during mandibular distraction osteogenesis in rabbits and also investigated the mechanism of membranous bone distraction. MATERIALS AND METHODS: Twenty-three rabbits underwent mandibular distraction (protocol; no latency period, a 1-week distraction at 0.5 mm/d, and a 2-week consolidation period). Samples were collected at 3, 5, and 7 days of distraction and at 1-week and 2-week consolidation. We prepared undecalcified fresh-frozen sections and immunohistochemically evaluated the expression of BMPs 2 through 8. RESULTS: Both endochondral ossification and intramembranous ossification were observed. The expression of BMPs 2, 4, 5, and 6 was observed continuously from the beginning of distraction. BMP-7 was expressed weakly. The expression of BMP-3 was not observed conspicuously during distraction but was strongly expressed at 1- and 2-week consolidation. CONCLUSION: The expression pattern of BMPs during membranous bone distraction was similar to that during long bone distraction, but it differed from the expression pattern of long bone distraction in that the expression of BMPs was maintained for 2 weeks after the completion of distraction.

Animals↗
PubMed1990

Radiation-sterilized insoluble collagenous bone matrix is a functional carrier of osteogenin for bone induction.

The influence of gamma radiation on the role of the collagenous substratum as a carrier for proteins which cause bone induction was examined. Osteoinductive demineralized bone matrix was extracted by 4 M guanidinium hydrochloride. The insoluble collagenous bone matrix (ICBM) obtained was not osteoinductive; however, when reconstituted with partially purified osteogenin, bone induction was restored. In order to apply the principle of bone induction to clinical use, methods of sterilization must be optimized to maintain the osteoinductive activity of bone allografts. The inactive substratum was irradiated and reconstituted with an active, partially purified bone extract and bioassayed. Irradiation of the ICBM by a Cobalt 60 source at a dose of 1 and 3 Mrads had no deleterious effect on the functional role of the substratum.

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

Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans.

Bone- and cartilage-derived morphogenetic proteins (BMPs and CDMPs), which are TGFbeta superfamily members, are growth and differentiation factors that have been recently isolated, cloned and biologically characterized. They are important regulators of key events in the processes of bone formation during embryogenesis, postnatal growth, remodelling and regeneration of the skeleton. In the present study, we used immunohistochemical methods to investigate the distribution of BMP-2, -3, -5, -6, -7 and CDMP-1, -2, -3 in human osteophytes (abnormal bony outgrowths) isolated from osteoarthritic hip and knee joints from patients undergoing total joint replacement surgery. All osteophytes consisted of three different areas of active bone formation: (1) endochondral bone formation within cartilage residues; (2) intramembranous bone formation within the fibrous tissue cover and (3) bone formation within bone marrow spaces. The immunohistochemistry of certain BMPs and CDMPs in each of these three different bone formation sites was determined. The results indicate that each BMP has a distinct pattern of distribution. Immunoreactivity for BMP-2 was observed in fibrous tissue matrix as well as in osteoblasts; BMP-3 was mainly present in osteoblasts; BMP-6 was restricted to young osteocytes and bone matrix; BMP-7 was observed in hypertrophic chondrocytes, osteoblasts and young osteocytes of both endochondral and intramembranous bone formation sites. CDMP-1, -2 and -3 were strongly expressed in all cartilage cells. Surprisingly, BMP-3 and -6 were found in osteoclasts at the sites of bone resorption. Since a similar distribution pattern of bone morphogenetic proteins was observed during embryonal bone development, it is suggested that osteophyte formation is regulated by the same molecular mechanism as normal bone during embryogenesis.

Aged↗
PubMed1999

Localization of a locus responsible for the bovine chondrodysplastic dwarfism (bcd) on chromosome 6.

A hereditary chondrodysplastic dwarfism caused by an autosomal recessive gene has been reported in a population of Japanese Brown cattle. Affected calves show an insufficiency of endochondral ossification at the long bones of the limbs. In the present study, we mapped the locus responsible for the disease (bcd) by linkage analysis, using microsatellite markers and a single paternal half-sib pedigree obtained from commercial herds. Linkage analysis revealed a significant linkage between the bcd locus and marker loci on the distal region of bovine Chromosome (Chr) 6. The bcd locus was mapped in the interval between microsatellite markers BM9257 and BP7 or BMS511 with a recombination fraction of 0.05 and 0.06, and a lod score of 8.6 and 10.1, respectively. A comparison of genetic maps between bovine Chr 6 and human Chr 4 or mouse Chr 5 indicates possible candidate genes including FGFR3 and BMP3 genes, which are responsible for human chondrodysplasias and associated with bone morphogenesis, respectively.

Animals↗
PubMed1990

Repair of calvarial nonunions by osteogenin, a bone-inductive protein.

Efforts were taken to determine the dose of bovine osteogenin (OG) that would induce more bone than that induced by 20 mg of rat particulate demineralized bone matrix (DBM), the amount allowed by the confines of an 8-mm rat craniotomy defect. Dose-response studies were performed for demineralized bone matrix alone and osteogenin, partially purified from bovine demineralized bone matrix, plus rat insoluble collagenous bone matrix (M). Demineralized bone matrix alone (2.5, 5.0, 10, 20, or 40 mg) or osteogenin (0.0625, 0.125, 0.250, 0.50, or 1.0 mg) plus 25 mg insoluble collagenous bone matrix was implanted into the pectoralis muscle for 3, 5, and 7 weeks. Both materials induced time- and dose-dependent formation of bone. The three highest dosages of osteogenin (plus insoluble collagenous bone matrix) induced more bone than 20 mg demineralized bone matrix and seemed to accelerate bone repair. However, when implanted into the 8-mm rat craniotomy defect for 4 weeks, 20 mg demineralized bone matrix and 0.5 mg osteogenin (plus insoluble collagenous bone matrix) induced comparable amounts of bone. These results suggest different mechanisms for bone formation in heterotopic and orthotopic sites.

Animals↗
PubMed1994

Osteogenin (bone morphogenic protein 3) inhibits proliferation and stimulates differentiation of osteoprogenitors in human bone marrow.

Treatment of human bone marrow osteoprogenitors with osteogenin (BMP-3; at 1, 2.5 and 10 ng/ml) caused dose- and time-dependent inhibition of DNA synthesis and cell proliferation. Simultaneously, osteogenin stimulated type I collagen synthesis and cAMP production. Addition of osteogenin to the cell culture increased intracellular alkaline phosphatase activity and osteocalcin synthesis, with maximal stimulation at 2.5 ng/ml. Simultaneous addition of 2.5 ng/ml osteogenin and 1,25 dihydroxy vitamin D3 (10(-8) M) enhanced the stimulation observed in osteocalcin synthesis. The experiments reported here demonstrate the significant "in vitro" influence of osteogenin in the stimulation of osteogenic phenotype in osteoprogenitor cells which have been isolated from human bone marrow and cloned. These results support a reciprocal relationship between cell growth inhibition and expression of osteoblast differentiation.

Adult↗
PubMed1995

Tricalcium phosphate and osteogenin: a bioactive onlay bone graft substitute.

The disadvantages of autogenous bone grafts has prompted a search for a dependable onlay bone graft substitute. A combination of tricalcium phosphate, a resorbable ceramic, and osteogenin, an osteoinductive protein, was evaluated as an onlay bone graft substitute in a rabbit calvarial model. Twenty-eight tricalcium phosphate implants (15 mm diameter x 5 mm; pore size, 100-200 microns) were divided into experimental and control groups and placed on the frontal bone of 14 adult New Zealand White rabbits. In the experimental animals, 185 micrograms of osteogenin was added to each implant. In the control animals, the implants were placed untreated. Implants were harvested at intervals of 1, 3, and 6 months, and evaluated using hematoxylin and eosin histology, microradiography, and histomorphometric scanning electron microscope backscatter image analysis. At 1 month there was minimal bone ingrowth and little tricalcium phosphate resorption in both the osteogenin-treated and control implants. At 3 months, both the osteogenin-treated and control implants showed a modest increase in bone ingrowth (8.85 percent versus 5.87 percent) and decrease in tricalcium phosphate (32.86 percent versus 37.08 percent). At 6 months, however, the osteogenin-treated implants showed a statistically significant increase in bone ingrowth (22.33 percent versus 6.96 percent; p = 0.000) and decrease in tricalcium phosphate (27.25 percent versus 37.80 percent; p = 0.004) compared with the control implants. The bone within the control implants was mostly woven at 6 months, whereas the osteogenin-treated implants contained predominantly mature lamellar bone with well-differentiated marrow. All implants maintained their original volume at each time interval studied. The tricalcium phosphate/osteogenin composite, having the advantage of maintaining its volume and being replaced by new bone as the tricalcium phosphate resorbs, may be applicable clinically as an onlay bone graft substitute.

Animals↗
PubMed1993

Temporal changes during bone regeneration in the calvarium induced by osteogenin.

Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of defects treated with either rat insoluble collagenous bone matrix (ICBM) or partially purified bovine osteogenin, a bone-inductive protein, reconstituted with ICBM (OG/ICBM). Repair of all defects was similar histologically throughout the first 3 days, characterized by acute, then chronic inflammation and granulation tissue formation. In defects treated with OG/ICBM, cartilage and osteoblasts were present at day 5. By day 9, cartilage and osteoid production were active. New bone showed hematopoietic tissue by day 11; a complete bone bridge was established by day 21. By day 42, fatty marrow was present. Defects treated with ICBM alone showed islands of cartilage and bone embedded in connective tissue at day 9, which reached peak maturity by day 14. In these and in untreated defects, significant osteoblastic and osteoclastic activity, located primarily at the margins of the defects, subsided by day 28. Untreated defects gradually filed in with fibrous connective tissue which matured throughout 156 days. Radiopacity, quantified by computerized image analysis, increased significantly between days 9 and 11 in OG/ICBM-treated defects, and remained greater (P < 0.05) than that of the ICBM-treated defects. There was a more gradual increase in radiopacity in ICBM-treated defects. The sequence of morphologic events during calvarial bone regeneration was very similar to that described previously for heterotopic bone formation induced by demineralized bone matrix.

Animals↗
PubMed1996

Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos.

Bone morphogenetic protein-3 (BMP-3) and BMP-7 are members of the transforming growth factor beta superfamily that have been implicated in the formation of cartilage and bone. Using in situ hybridization, we localized mRNAs for BMP-3 and BMP-7 during organogenesis in rats. Both mRNAs were expressed in a variety of cells, in particular, in the developing hair follicle, tooth, kidney, and lung tissues, in which reciprocal epithelial-mesenchymal interactions are essential. In some tissues, the distribution of BMP-3 and BMP-7 mRNAs overlapped. In other tissues, the patterns of expression were quite different. Moreover, the site of expression of the transcripts changed from one cell type to another during organogenesis. These results suggest that BMP-3 and BMP-7 play important roles in organogenesis and that the differential patterns of their expression might reflect their distinct roles in embryogenesis.

Adrenal Glands↗
PubMed1999

Localized expression of BMP and GDF mRNA in the rodent brain.

Expression of BMP- and GDF-related factors within the transforming growth factor-beta (TGF-beta) superfamily was examined in the rat and mouse brain by in situ hybridization. Strong signals were obtained in neurons for GDF-1 and GDF-10. GDF-1 is expressed at postnatal day 6 in the cerebral cortex, hippocampal CA1 through CA3 neurons, while only weakly expressed by cells in the dentate gyrus. Granule cells and neurons in the polymorph layer of the dentate gyrus are GDF-1-positive, as are the majority of neurons in the cortex. GDF-10 shows a distinct pattern of expression: At P6, strong labelling was seen in the superficial layers of cortex, notably in the posterior cingulate cortex, and in CA3 and dentate gyrus. From postnatal day 21, GDF-1 expression is strong in the hippocampus, cortex, and thalamic nuclei, while GDF-10 expression becomes restricted to the granule cell layer in the dentate gyrus. In contrast, OP-1 expression is restricted throughout development to cells of the medial habenular nucleus, choroid plexus, and leptomeninges. The markedly different expression patterns of these BMPs suggest they serve separate functions in the brain.

Aging↗
PubMed1996

Dexamethasone regulation of marrow stromal-derived osteoblastic cells.

The clonal subtypes of cells in the osteogenic family represented by fibroblastoid MBA-15.33, preosteoblast MBA-15.4, and mature osteoblastic MBA-15.6 cells were used to study the effects of glucocorticoid (dexamethasone). The role of dexamethasone was monitored on cell attachment when plated on various protein substrata (BSA, collagen 1, and Matrigel). A 24 h exposure of the cells to 10(-6) M or 10(-7) M dexamethasone differential affects their attachment preference. MBA-15.33 and MBA-15.4 cells increased their attachment capability on collagen 1, while MBA-15.6 cells' attachment was inhibited. Pretreatment with (10(-6) M) dexamethasone caused an increase in attachment on Matrigel by MBA-15.33 cells and to less extent by MBA-15.4 cells. Additionally, measurements of two enzymatic activities were monitored; one is alkaline phosphatase (ALK-P), and the second is neutral endopeptidase (CD10/NEP). MBA-15.33, MBA-15.4, and MBA-15.6 cells were exposed to dexamethasone or to various growth factors (bone morphogenic protein (BMP-2 and BMP-3), TGF beta, and IGF-1). In some experiments, pretreatment of cells by dexamethasone was followed by exposure to the growth factors. The cells' challenged cellular responses were not uniform and revealed a differential pattern when their ALK-P and CD10/NEP enzymatic activities were measured.

Animals↗
PubMed1999

Effect of 1,25(OH)2D3 on bone morphogenetic protein-3 mRNA expression.

Bone morphogenetic proteins (BMPs) are members to the transforming growth factor-beta superfamily. They induce ectopic bone formation in rat and are pleiotropic initiators of inducible osteogenic precursor cells. A lot of reports have studied the presence of BMPs and their effects on bone marker expression in many different cell lines, however none describe the regulation of BMP3 by different factors and expression conditions. When a human bone marrow stromal cell (HBMSC) culture was treated simultaneously with 1,25(OH)2D3 (10(-8) M) and BMP3 (2.5 ng/ml), the total osteocalcin content in the cell layer and in the culture medium was higher than when the culture was treated with either factor alone (162%). To elucidate this synergistic activity, Northern blot analysis was done to study the effect of 1,25(OH)2D3 on BMP3 mRNA expression. Several human cell lines (MNNG, U-2OS, MG-63, KHOS, TE85, HOS) and HBMSC were treated by 1,25(OH)2D3 (10(-8) M for 24 h). Purified mRNA from treated and untreated cells were denatured using glyoxal and dimethylsulfoxide, and were fractionated on a 1% agarose gel. After electrophoresis, RNA were blotted onto a nylon membrane and incubated with 32P-labeled BMP3 and GAPDH riboprobes. Northern blot analysis revealed that, the BMP3 mRNA level was increased in a few cell lines (MG-63, HBMSC, HOS) after the addition of 1,25(OH)2D3 when compared to the untreated cells (127%+/-1; 130.5%+/-19.5; 207%+/-14). An higher stimulation was observed in HBMSC primary culture when compared to differentiated HBMSC. In view of these results, we now investigate the following hypothesis: does the BMP3 promoter exhibit the vitamin D receptor response like the osteocalcin gene?

Bone Morphogenetic Protein 3↗