Aims: Osteoclasts, the unique bone-resorbing polykaryons, are responsible for many bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Hence, the regulation of osteoclast formation is considered a potential therapeutic approach for these diseases. In this study, we investigated the effect of a novel small compound, C(25)H(32)N(4)O(4)S(2) (NecroX-7) on osteoclast formation.
Main methods: We analyzed the effects of NecoX-7 on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation in vitro and LPS-induced bone loss in vivo.
Key findings: We observed that NecroX-7 suppressed osteoclast formation from primary bone marrow macrophages (BMMs) in a dose-dependent manner. NecroX-7 significantly inhibited the NF-κB signaling pathway without affecting the activation of the mitogen-activated protein kinases (MAPKs) JNK, p38, and ERK in response to RANKL. In addition, NecroX-7 strongly attenuated the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are crucial transcription factors for osteoclast differentiation. Mirroring the down-regulation of c-Fos and NFATc1, the expression of osteoclastogenic markers, such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K, was also reduced by the addition of NecroX-7. Furthermore, confirming the in vitro anti-osteoclastogenic effect, NecroX-7 inhibited lipopolysaccharide (LPS)-induced bone loss in vivo.
Significance: Our data imply that NecroX-7 is useful as a therapeutic drug for the treatment of bone resorption-associated diseases.
Copyright © 2012 Elsevier Inc. All rights reserved.