Institution: | 1. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China
Department of Trauma Orthopedic and Hand Surgery, Research Centre for Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Li and Xiao are co-first authors and contributed equally to this work.;2. School of Biomedical Sciences, the University of Western Australia, Perth, Western Australia, Australia;3. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China;4. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China
School of Biomedical Sciences, the University of Western Australia, Perth, Western Australia, Australia;5. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China
Department of Trauma Orthopedic and Hand Surgery, Research Centre for Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China;6. Department of Trauma Orthopedic and Hand Surgery, Research Centre for Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China |
Abstract: | Osteoporosis is a class of metabolic bone disease caused by complexed ramifications. Overactivation of osteoclasts due to a sudden decreased estrogen level plays a pivotal role for postmenopausal women suffering from osteoporosis. Therefore, inhibiting osteoclast formation and function has become a major direction for the treatment of osteoporosis. Tiliroside (Tle) is a salutary dietary glycosidic flavonoid extracted from Oriental Paperbush flower, which has been reported to have an anti-inflammation effect. However, whether Tle affects the osteoclastogenesis and bone resorption remains unknown. Herein, we demonstrate that Tle prevents bone loss in ovariectomy in mice and inhibits osteoclast differentiation and bone resorption stimulated by receptor activator of nuclear factor-κB ligand (RANKL) in vitro. Molecular mechanism studies reveal that Tle reduces RANKL-induced activation of mitogen-activated protein kinase and T-cell nuclear factor 1 pathways, and osteoclastogenesis-related marker gene expression, including cathepsin K (Ctsk), matrix metalloproteinase 9, tartrate-resistant acid phosphatase (Acp5), and Atp6v0d2. Our research indicates that Tle suppresses osteoclastogenesis and bone loss by downregulating the RANKL-mediated signaling protein activation and expression. In addition, Tle inhibits intracellular reactive oxygen species generation which is related to the formation of osteoclasts. Therefore, Tle might serve as a potential drug for osteolytic disease such as osteoporosis. |