Sphingomyelinase and ceramide inhibit formation of F-actin ring in and bone resorption by rabbit mature osteoclasts.

Recent studies have demonstrated that ceramide plays an important role as a second messenger in many kinds of cells. However, it is not known whether apoptosis of and bone resorption by mature osteoclasts are mediated via sphingomyelinase (SMase) and ceramide. Thus, we examined the possible involvement of SMase and ceramide in the induction of apoptosis in and bone resorption by rabbit mature osteoclasts. SMase and C2-ceramide inhibited strongly F-actin ring formation of and bone resorption by the osteoclasts. However, the osteoclast apoptosis was not induced by C2-ceramide. The ceramide inhibition of the bone resorption was suppressed by DL-threodihydrosphingosine, an inhibitor of sphingosine kinase. In addition, we observed that sphingosine-1-phosphate is able to inhibit bone resorption by the osteoclasts. These results suggest an important role of the sphingomyelin pathway in bone resorption by rabbit mature osteoclasts.