The Role of Adseverin in RANKL-Induced Osteoclastogenesis

Abstract

Adseverin, a member of the gelsolin superfamily of actin binding proteins, is a Ca2+-dependent actin filament-severing protein. The role of adseverin has been reported about exocytosis regulation through actin cytoskeleton rearrangement in secretory cells. However, the function of adsevrin in bone still remains unclear, and it has not yet been examined in osteoclastogenesis. Here, I investigated the role of adseverin in osteoclastogenesis using bone marrow-derived macrophages (BMMs). I found that expression of the adseverin gene, scinderin, was up-regulated during RANKL-induced osteoclast differentiation. Knock-down of adseverin significantly blocked the increase of nuclear factor of activated T cell c1 (NFATc1), which is a key regulator of osteoclastogenesis and also decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs). In addition, adseverin deficiency impaired the resorption activity and the secretion of bone degrading enzymes in osteoclast. These phenomenons were caused by decreased NFATc1 expression through NF-B signaling. Collectively, these findings indicate that adseverin plays an important role in osteoclastogenesis via regulation of NFATc1 expression.