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 know n whether apoptosis of and bone resorption by mature osteoclasts are m ediated via sphingomyelinase (SMase) and ceramide. Thus, we examined t he possible involvement of SMase and ceramide in the induction of apop tosis in and bone resorption by rabbit mature osteoclasts. SMase and C 2-ceramide inhibited strongly F-actin ring formation of and bone resor ption by the osteoclasts. However, the osteoclast apoptosis was not in duced by C2-ceramide. The ceramide inhibition of the bone resorption w as suppressed by DL-threo-dihydrosphingosine, an inhibitor of sphingos ine kinase. In addition, we observed that sphingosine-l-phosphate is a ble to inhibit bone resorption by the osteoclasts. These results sugge st an important role of the sphingomyelin pathway in bone resorption b y rabbit mature osteoclasts. (C) 1998 Federation of European Biochemic al Societies.