Chemotactic activity of theγ-carboxyglutamic acid containing protein in bone

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Abstract
We have found that theγ-carboxyglutamic acid (GLA)-containing protein from bone (BGP, osteocalcin) has chemotactic activityin vitro for a number of cells which are found adjacent to endosteal bone surfacesin vivo. Using the Boyden chamber technique for measuring cell chemotaxisin vitro, we have shown that BGP is chemotactic for cultured human breast cancer cells, human and mouse monocytes, and for cultured rat osteosarcoma cells which have the characteristics of osteoblasts. The migration of these cells in response to BGP is unidirectional and not due to spontaneous or random migration. A synthetic peptide (Phe-Tyr-Gly-Pro-Val), which is identical to the carboxyterminal peptide cleaved from BGP when digested by trypsin, is also chemotactic for the same cells. BGP retains its chemotactic activity after conversion of theγ-carboxyglutamic acid residues to glutamic acid, indicating that this biological effect requires neitherγ-carboxyglutamate nor the ability of BGP to bind calcium. Since BGP is released from bone during states of increased bone turnover, it is possible that this chemotactic effect of the protein may be a mechanism for recruitment of these cells to sites of active bone remodeling.