kirenol and Osteoporosis

Osteoporosis is a threat to aged people who have excessive osteoclast activation and bone resorption, subsequently causing fracture and even disability. Inhibiting osteoclast differentiation and absorptive functions has become an efficient approach to treat osteoporosis, but osteoclast-targeting inhibitors available clinically remain rare. Kirenol (Kir), a bioactive diterpenoid derived from an antirheumatic Chinese herbal medicine Herba Siegesbeckiae, can treat collagen-induced arthritis in vivo and promote osteoblast differentiation in vitro, while the effects of Kir on osteoclasts are still unclear.. We explore the role of Kir on RANKL-induced osteoclastogenesis in vitro and bone loss in vivo.. The in vitro effects of Kir on osteoclast differentiation, bone resorption and the underlying mechanisms were evaluated with bone marrow-derived macrophages (BMMs). In vivo experiments were performed using an ovariectomy (OVX)-induced osteoporosis model.. Kir suppresses osteoclastogenesis and the Cav-1/NFATc1 signaling pathway both in vitro and in vivo and protects against OVX-induced osteoporosis. Our findings reveal Kir as a potential safe oral treatment for osteoporosis.

Topics: Administration, Oral; Animals; Bone Resorption; Calcium; Caveolin 1; Cell Differentiation; Diterpenes; Female; Macrophages; Mice, Inbred C57BL; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; RANK Ligand; Signal Transduction