Chick osteocyte-derived protein inhibits osteoclastic bone resorption

Abstract

In order to investigate the role of osteocytes in bone resorption, we examined the homogenate and conditioned medium from purified chick calvarial osteocytes in a pit-formation assay using unfractionated bone cells from mice. The osteocyte homogenate markedly inhibited pit formation, whereas the conditioned medium of osteocytes had no effect. This inhibitory activity was not the result of cytotoxicity of the homogenate. A novel bone-resorption-inhibitory protein was purified from collagenase-digested chick calvarial fragments enriched in osteocytes. The inhibitory protein, of molecular mass 18.5 kDa, showed significant dose-dependent inhibition of pit formation by unfractionated bone cells from mice and rabbits, and by human giant tumour cells. This protein also inhibited the bone-resorbing activity of purified osteoclasts in the pit-formation assay in the absence of other effector cells. Microinjection of the protein into osteoclasts caused disruption of the podosomes 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.

Osteocytes inhibit osteoclastic bone resorption through transforming growth factor‐β: Enhancement by estrogen*

“…Thus, it is dif®cult to have a straight comparison with other studies. Maejima-Ikeda et al [1997] have described an 18.5-kDa chick osteocytederived protein that inhibited osteoclastic bone resorption. They used mouse, rabbit, or human giant tumor cell osteoclasts for bone resorption assay but did not see any effect with primary chick osteocyte CM.…”

Post-Extraction Remodeling of the Adult Mandible

“…Osteocytes are thought by some to be the cells responsible for detecting and initiating the cellular responses to changes in bone function, but a large number of osteocytes die following tooth extraction, resulting in many cell-free areas of bone in the initial stages of socket healing . These dead cells may account, in part, for the initial rapid phase of remodeling that is seen after tooth loss, since live osteocytes may release factors that inhibit osteoclasis (Maejima-Ikeda et al, 1997;.…”

Apoptotic Bodies Convey Activity Capable of Initiating Osteoclastogenesis and Localized Bone Destruction

“…Potential osteocyte-related molecular mechanisms capable of controlling targeted bone resorption include either the loss of antiresorptive signals (11)(12)(13) or the gain of proresorptive signals. (14) Because bone containing low numbers of viable osteocytes is not readily remodeled (15)(16)(17)(18)(19) and osteocytes are, in vitro, known to be associated with proosteoclastogenic activity, (20) it seems likely that osteocytes produce pro-rather than antiresorptive signals.…”