Endogenous Inhibitor of Bone Cell Proliferation

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Abstract
A substance recovered from the medium of embryonic chick bones growing in organ culture inhibits the proliferation of chick calvarial bone cells in vitro. This inhibition of proliferation occurs within 3 h after exposure of the cells to the inhibitory substance (IS) in a manner which does not appear to affect the protein synthesis or the gross morphology of the cells. The medium from which IS is obtained can be diluted 500-x and still retain significant inhibitory activity. Cells in culture spontaneously escape the inhibition of a single dose of IS within 24 h of exposure: upon further addition of IS to thses cells inhibition of proliferation is again observed. Cells derived from chick bone and rat and human bone are more sensitive to the inhibition than are chick dermal fibroblasts and chick liver and muscle cells. IS is not destroyed after treatment of the conditioned medium with trypsin, phospholipase A2, RNase, neuraminidase or heat. IS is also not a commonly produced prostaglandin. Estimates of the MW of IS range from 6000 to 14,000 daltons. While these features do not disclose the exact nature of this substance, they are consistent with this substance being a small polypeptide without the exposed amino acids, lysine or arginine. The presence of such a substance supports the concept of local regulation of bone metabolism.

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