Summary
Subcutaneous implantation of demineralized bone matrix induces the local formation of cartilage and bone. In this study we have investigated the influence of adding various growth factors to the implant. Cartilage formation was monitored by measuring collagen II mRNA levels, and bone formation in the implant was assessed from alkaline phosphatase activity and calcium content. Supplements of the platelet-derived growth factor to implants in older rats increased and production of mRNA for collagen II, alkaline phosphatase activity, and the calcium content of the implant, whereas the other growth factors tested were without effect. The data suggest that under some conditions bone induction is submaximal and can be increased by local supplement of platelet-derived growth factor (PDGF). The present observations may have important therapeutic implications in the treatment of nonunions of fractures and impaired bone formation in the aged.
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References
Urist MR (1965) Bone: formation by autoinduction. Science 150:893–899
Reddi AH, Huggins CB (1972) Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci USA 69:1601–1605
Reddi AH, Anderson WA (1976) Collagenous bone matrix-induced endochondral ossification and hematopoiesis. J Cell Biol 69:557–572
Reddi AH (1981) Cell biology and biochemistry of endochondral bone development. Collagen Res 1:209–226
Somerman M, Hewitt AT, Varner HH, Schiffmann E, Termine J, Reddi AH (1983) Identification of a bone matrix-derived chemotactic factor. Calcif Tissue Int 35:481–485
Rath NC, Reddi AH (1979) Collagenous bone matrix is a local mitogen. Nature 278:855–857
Sampath TK, DeSimone DP, Reddi AH (1982) Extracellular bone matrix-derived growth factor. Exp Cell Res 142:460–464
Ross R (1969) Wound healing. Scientific American 220:40–50
Hunt TK, Knighton DR, Thakral KK, Andrews W, Michaeli D (1984) Cellular control of repair. In: Hunt TK, Heppenstall RB, Pines E, Rovee D (eds) Soft and hard tissue repair. Praeger, New York, pp 3–19
Grotendorst GR, Pencev D, Martin GR, Sodek J (1984) Molecular mediators of tissue repair. In: Hunt TK, Heppenstall RB, Pines E, Rovee D (eds) Soft and hard tissue repair. Praeger, New York, pp 20–40
Sporn MB, Roberts AB, Shall JH, Smith JM, Ward JM, Sodek J (1983) Polypeptide-transforming growth factors isolated from bone sources and used for wound healing in vivo. Science 219:1329–1331
Buckley A, Davidson JM, Kamerath CD, Wolt TB, Woodword SC (1985) Sustained release of epidermal growth factor accelerates wound repair. Proc Natl Acad Sci USA, 82:7340–7344
Grotendorst GR, Martin GR, Pencev D, Sodek J, Harvey AK (1985) Stimulation in granulation tissue formation by platelet-derived growth factor in normal diabetic rats. J Clin Invest 76:2323–2329
Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R (1985) A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell 43:277–286
Martinet Y, Bitterman PB, Mornex JF, Grotendorst GR, Martin GR, Crystal RG (1986) Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature 319:158–160
Reddi AH, Sullivan NE (1980) Matrix-induced endochondral bone differentiation: influence of hypophysectomy. Growth hormone and thyroid-stimulating hormone. Endocrinology 107:1291–1299
Jonas E, Sargent TD, Dawid IB (1985) Epidermal keratin gene expressed in embryos ofXenopus laevis. Proc Natl Acad Sci USA 82:5413–5417
Halliburton EW, Thomson RY (1965) Chemical aspects of compensatory renal hypertrophy. Cancer Res 25:1882–1887
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1954) Protein measurement with the Folin phenol reagent. J Biol Chem 193:205–215
Church G, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci 81:1991–1995
Kohno K, Martin GR, Yamada Y (1984) Isolation and characterization of a cDNA clone for the amino terminal portion of pro α1 (II) chain of cartilage collagen. J Biol Chem 259:13668–13673
Grotendorst G (1984) Alteration of the chemotactic response of NIH/3T3 cells to PDGF by growth factors, transformation, and tumor promoters. Cell 36:279–285
Reddi AH (1985) Regulation of bone differentiation by local and systemic factors. Bone and Mineral Res 3:27–47
Canalis E (1981) Effect of platelet-derived growth factor on DNA and protein synthesis in cultured rat calvaria. Metabolism 30:970–975
Tashjian AH, Hohmann EL, Antoniades HN, Levine L (1982) Platelet-derived growth factor stimulates bone resorption via a prostaglandin-mediated mechanism. Entochinologh 111:118–124
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Howes, R., Bowness, J.M., Grotendorst, G.R. et al. Platelet-derived growth factor enhances demineralized bone matrix-induced cartilage and bone formation. Calcif Tissue Int 42, 34–38 (1988). https://doi.org/10.1007/BF02555836
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DOI: https://doi.org/10.1007/BF02555836