CHICK OSTEOCYTE-DERIVED PROTEIN INHIBITS OSTEOCLASTIC BONE-RESORPTION

In order to investigate the role of osteocytes in bone resorption, we examined the homogenate and conditioned medium from purified chick cal varial osteocytes in a pit-formation assay using unfractionated bone c ells from mice. The osteocyte homogenate markedly inhibited pit format ion, whereas the conditioned medium of osteocytes had no effect. This inhibitory activity was not the result of cytotoxicity of the homogena te. A novel bone-resorption-inhibitory protein was purified from colla genase-digested chick calvarial fragments enriched in osteocytes. The inhibitory protein, of molecular mass 18.5 kDa, showed significant dos e-dependent inhibition of pit formation by unfractionated bone cells f rom mice and rabbits, and by human giant tumour cells. This protein al so inhibited the bone-resorbing activity of purified osteoclasts in th e pit-formation assay in the absence of other effector cells. Microinj ection of the protein into osteoclasts caused disruption of the podoso mes in the cells. The N-terminal 25-amino-acid sequence of the protein showed 68% identity to a part of Rho-GTP-dissociation inhibitor. Thus chick calvarial osteocytes may be involved in the regulation of bone resorption by osteoclasts.