Effects of NSAIDs on Differentiation and Function of Human and Murine Osteoclasts – Crucial ‘Human Osteoclastology’.docVIP

Pharmaceuticals2010, 3, 1394-1410; doi:10.3390/ph3051394 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Effects of NSAIDs on Differentiation and Function of Human and Murine Osteoclasts – Crucial ‘Human Osteoclastology’ Shigeru Kotake *, Toru Yago, Manabu Kawamoto and Yuki Nanke Institute of Rheumatology, Tokyo Womens Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan; E-Mails: toruyago@yahoo.co.jp (T.Y.); kawamoto@ior.twmu.ac.jp (M.K.); ynn@ior.twmu.ac.jp (Y.N.) * Author to whom correspondence should be addressed; E-Mail: skotake@ior.twmu.ac.jp; Tel.: +81-3-5269-1725; Fax: +81-3-5269-1726. Received: 01 April 2010; in revised form: 21 April 2010 / Accepted: 29 April 2010 / Published: 11 May 2010 Abstract: Osteoclasts play a critical role in both normal bone metabolism and bone resorption in the joints of patients with rheumatoid arthritis. It has been reported that non- steroidal anti-inflammatory drugs (NSAIDs) inhibit murine osteoclastogenesis in vitro and murine arthritis models in vivo, but not the destruction of joints of patients with rheumatoid arthritis. In the current review article, we review the recent findings in the effect of NSAIDs on the formation and function of human and murine osteoclasts both in vitro and in vivo, underlining the importance of studies using human osteoclasts. Since 2009, we have suggested a novel term ‘human osteoclastology’. Keywords: non-steroidal anti-inflammatory drugs (NSAIDs); osteoclast; osteo- clastogenesis; osteoclastology; prostaglandin E2 (PGE2); interleukin-17 (IL-17) 1. Introduction Many studies have investigated the hypothesis that activated T cells directly or indirectly modulate the formation and function of osteoclasts in bone resorption associated with rheumatoid arthritis (RA) since the receptor activator of NF-κB ligand (RANKL) was cloned as a factor inducing osteoc