Stimulation of the expression of osteogenic and chondrogenic phenotypes in vitro by osteogenin.
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Osteogenin was recently purified and the amino acid sequences of tryptic peptides were determined. Osteogenin in conjunction with insoluble collagenous bone matrix induces cartilage and bone formation in vivo. To understand the mechanism of action of osteogenin, we examined its influence on periosteal cells, osteoblasts, fibroblasts, chondrocytes, and bone marrow stromal cells in vitro. Osteogenin stimulated alkaline phosphatase activity and collagen synthesis in periosteal cells. The cAMP response to parathyroid hormone in periosteal cells was increased by osteogenin. In primary cultures of calvarial osteoblasts, osteogenin stimulated alkaline phosphatase activity, the cAMP response to parathyroid hormone, and the synthesis of collagenous and noncollagenous proteins; however, cell proliferation was not affected. Osteogenin increased the production of sulfated proteoglycans in fetal rat chondroblasts and in rabbit articular chondrocytes. The present experiments demonstrate the significant influence of osteogenin in the stimulation of osteogenic and chondrogenic phenotypes in vitro. (+info)
Platelet-derived growth factor inhibits bone regeneration induced by osteogenin, a bone morphogenetic protein, in rat craniotomy defects.
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Platelet-derived growth factor (PDGF) is a potent moderator of soft tissue repair through induction of the inflammatory phase of repair and subsequent enhanced collagen deposition. We examined the effect of recombinant BB homodimer PDGF (rPDGF-BB) applied to rat craniotomy defects, treated with and without bovine osteogenin (OG), to see if bone regeneration would be stimulated. Implants containing 0, 20, 60, or 200 micrograms rPDGF-BB, reconstituted with insoluble rat collagenous bone matrix containing 0, 30, or 150 micrograms OG, were placed into 8-mm craniotomies. After 11 d, 21 of the 144 rats presented subcutaneous masses superior to the defect sites. The masses, comprised of serosanguinous fluid encapsulated by fibrous connective tissue, were larger and occurred more frequently in rats treated with 200 micrograms rPDGF-BB, and were absent in rats not treated with rPDGF-BB. The masses underwent resorption within 28 d after surgery. OG (2-256 micrograms) caused a dose-dependent increase in radiopacity and a marked regeneration of calcified tissue in a dose-dependent fashion within defect sites. However, OG-induced bone regeneration was inhibited 17-53% in the presence of rPDGF-BB. These results suggest that rPDGF-BB inhibited OG-induced bone regeneration and stimulated a soft tissue repair wound phenotype and response. (+info)
Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos.
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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. (+info)