Wedelolactone exerts double protection for bones through enhancing osteoblastogenesis but inhibiting osteoclastogenesis

Abstract

Bone homeostasis is maintained by osteoclast-mediated bone destruction and osteoblast-mediated bone formation, which are two tightly coupled and controlled processes. Double protection for bones through enhancing osteoblastogenesis but inhibiting osteoclastogenesis becomes a promising strategy for treating osteoporosis. However, there are little small molecular compounds found to regulate bone remodeling balance. We recently examined the effect of wedelolactone, a natural product from Ecliptae herba , on osteoblastogenesis and osteoclastogenesis in vitro and in vivo. Our results revealed that wedelolactone stimulated osteoblast differentiation and bone mineralization in mouse bone marrow mesenchymal stem cells (BMSC). At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. The dual functional role of wedelolactone was mediated through inducing Wnt/GSK-3β/β-catenin pathway in BMSC and inhibiting NF-κB/c-fos/NFATc1 pathway in preosteoclastic RAW264.7 cells. Thus, we found that wedelolacone simultaneously regulated bone resorption and bone formation, and could therefore develop a new class of dual-action therapeutic agents for osteoporosis.