Protection against Ovariectomy-Induced Bone Loss by Tranilast.

Phan, Tien Van; Ke, Ke; Sul, Ok-Joo; Park, Yun-Kyung; Kim, Kack-Kyun; Cho, Yeon-Soo; Chung, Hun-Taeg; Choi, Hye-Seon

Background: Tranilast (N-(3′,4′-dimethoxycinnamonyl) anthranilic acid) has been shown to be therapeutically effective, exerting anti-inflammatory and anti-oxidative effects via acting on macrophage. We hypothesized that Tranilast may protect against oxidative stress-induced bone loss via action in osteoclasts (OCs) that shares precursors with macrophage. Methodology and Principal Findings: To elucidate the role of Tranilast, ovariectomy (OVX)-induced bone loss in vivo and OC differentiation in vitro were evaluated by µCT and tartrate-resistant acid phosphatase staining, respectively. Oral administration of Tranilast protected against OVX-induced bone loss with decreased serum level of reactive oxygen species (ROS) in mice. Tranilast inhibited OC formation in vitro. Decreased osteoclastogenesis by Tranilast was due to a defect of receptor activator of nuclear factor-κB ligand (RANKL) signaling, at least partly via decreased activation of nuclear factor-κB and reduced induction and nuclear translocation of nuclear factor of activated T cells, cytoplasmic 1 (or NFAT2). Tranilast also decreased RANKL-induced a long lasting ROS level as well as TGF-β to inhibit osteoclastogenesis. Reduced ROS caused by Tranilast was due to the induction of ROS scavenging enzymes (peroxiredoxin 1, heme oxygenase-1, and glutathione peroxidase 1) as well as impaired ROS generation. Conclusions/Significance: Our data suggests the therapeutic potential of Tranilast for amelioration of bone loss and oxidative stress due to loss of ovarian function.

OVARIECTOMY; AMINOBENZOIC acids; ANTI-inflammatory agents; MACROPHAGES; OXIDATIVE stress; PHARMACEUTICAL research

PLoS ONE, 2014, Vol 9, Issue 4, p1

1932-6203

Academic Journal

10.1371/journal.pone.0095585