Bioactive compounds suppressing differentiation of osteoclasts

Abstract

Bone formation and bone resorption are the processes which maintain bone homeostasis. The balance in functioning of osteoblasts and osteoclasts regulates bone remodeling. Dysregulated bone homeostasis results in bone diseases including osteoporosis. Therefore, osteoclasts are one of the target cells for anti-resorptive therapies to treat osteoporosis. To discover new anti-resorptive agents, we screened natural compounds from plants that inhibit osteoclastogenesis. In this study, we screened ten compounds from Kaempferia parviflora and six limonoid compounds from Xylocarpus moluccensis. We found that 7-oxo-deacetoxygedunin (7-OG), a limonoid compound from Xylocarpus moluccensis markedly inhibited the differentiation of osteoclasts induced by receptor activator of nuclear factor-кB ligand (RANKL). Treatment with 7-OG decreased the tartrate resistant acid phosphatase (TRAP) activity in pre-osteoclasts which was induced by RANKL in RAW264.7 cell line. The IC50 for cytotoxicity and anti-osteoclastogenic activity was more than 22.80 µM and 2.50 µM, respectively. We investigated the effects of 7-OG on the expression of osteoclast-related genes, NFATc1 and Cathepsin K, and found that treatment with 7-OG significantly suppressed the expression of both genes (p<0.05). Detailed analysis uncovered that 7-OG treatment suppressed the activation of NF-кB and MAPK signaling pathways. These results suggested that 7-OG inhibits osteoclastogenesis induced by RANKL by inferring with NF-кB and MAPK pathways and has potential to be a therapeutic agent for osteoporosis.