In vitro degradation of bone particles by human monocytes is decreased with the depletion of the vitamin K-dependent bone protein from the matrix

Abstract

The bone vitamin K-dependent protein osteocalcin has been suggested to play a role in bone resorption. By administering sodium warfarin to rats, it is possible to inhibit the vitamin K-dependent addition of the their gamma-carboxyglutamic acid residues to osteocalcin. This results in reduced amounts of osteocalcin bone, probably because devoid of the calcium-binding Gla residues, the protein no longer accumulates in bone. Preparations of bone obtained from rats treated with sodium warfarin for 6 weeks contained only 0.2% of normal levels of osteocalcin and were 90% reduced in the concentration of Gla. This bone could not be degraded by human monocytes in vitro as well as control bone (only 54% of control; P less than 0.003). Defects in the movement of cells to the bone were documented by phase contrast microscopy. Only 60% as many monocytes attached to the osteocalcin-depleted bone as to control bone in an in vitro attachment assay. These effects do not appear to be related to direct cellular toxicity. The degradation of bone in this in vitro system appears to be dependent on the osteocalcin content in matrix. This may result from defective movement of cells to bone and/or attachment to the bone.