Amlexanox Enforces Osteogenic Differentiation and Bone Homeostasis Through Inhibiting Ubiquitin-Dependent Degradation of β-Catenin
He Qian, Zhouboran Liu, Xuan Xia, Jun Zeng, Yuling Liu, Jing-qiong Xun, Meilu Liu, Yanrun Mei, Ru-Chun Dai
Abstract
knockdown promoted osteoblast differentiation. We explored amlexanox (AM), a novel IKKε inhibitor, for its effects on osteogenic differentiation and bone homeostasis. AM treatment in mice decreased bone loss, reduced marrow fat, and improved bone microarchitecture, leading to enhanced bone strength. In vitro, AM promoted osteogenesis and suppressed adipogenesis of BMSCs in a dose-dependent manner. Moreover, AM controlled RANKL/OPG expression of BMSC which regulated osteoclast differentiation. Mechanistic explorations revealed AM reinforced Wnt/β-catenin pathway by suppressing ubiquitin-proteasome-dependent degradation of β-catenin. Importantly, AM stimulated osteogenesis in human BMSCs. By promoting osteogenesis at the expense of adipogenesis and hindering osteoclastogenesis, AM offers a promising therapeutic strategy for osteoporosis due to its established safety profile.