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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 Dec;70(12 Pt 1-2):3511–3515. doi: 10.1073/pnas.70.12.3511

Bone Morphogenesis in Implants of Insoluble Bone Gelatin

Marshall R Urist 1, Hisashi Iwata 1, Peter L Ceccotti 1, Robert L Dorfman 1, Stuart D Boyd 1, Richard M McDowell 1, Constance Chien 1
PMCID: PMC427270  PMID: 4357876

Abstract

Insoluble bone gelatin with inclusions of insoluble noncollagenous protein produces new bone when implanted in muscle in allogeneic rats. The implanted residue provides the milieu for expression of bone morphogenetic potential of migratory mesenchymal cells. Neutral buffer solutions activate endogenous enzymes that degrade components essential for cell interactions and differentiation of bone. Chloroform-methanol either denatures or extracts constituents responsible for degradation. Insoluble bone gelatin produces new bone after extraction at 2° with neutral salts, 0.5 M EDTA, 0.1 M Tris·HCl, 4 M urea, 0.5 M hydroxylamine, and 10 M KCNS, as well as after limited digestion with pepsin or collagenase, but not after extraction with 5 M guanidine, 7 M urea, water saturated with phenol, or after alkali hydrolysis with 0.1 N NaOH. The specific activity of cell populations interacting with insoluble bone gelatin suggests that a chemical bond between collagen and a noncollagenous protein or part of a protein, cleaved by a neutral proteinase, controls the bone morphogenetic reaction.

Keywords: cell differentiation, osteogenesis, noncollagenous proteins

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Selected References

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