Chemotactic activity of the gamma-carboxyglutamic acid containing protein in bone.

We have found that the gamma-carboxyglutamic acid (GLA)-containing protein from bone (BGP, osteocalcin) has chemotactic activity in vitro for a number of cells which are found adjacent to endosteal bone surfaces in vivo. Using the Boyden chamber technique for measuring cell chemotaxis in 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 undirectional and not due to spontaneous or random migration. A synthetic peptide (Phe-Tyr-Gly-Pro-Val), which is identical to the carboxy-terminal peptide cleaved from BGP when digested by trypsin, is also chemotactic for the same cells. BGP retains its chemotactic activity after conversion of the gamma-carboxyglutamic acid residues to glutamic acid, indicating that this biological effect requires neither gamma-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.