Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 96, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107619
Keywords
Hinokitiol; Osteoclast; RANKL; MAPK; NFATc1
Categories
Funding
- National Natural Science Foundation of China, China [82072467, 81871801]
- Natural Science Foundation of Zhejiang Province, China [LQ21H060001]
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Hinokitiol was found to inhibit RANKL-induced osteoclast formation and bone resorption in vitro, and protected against ovariectomy-induced bone loss in vivo, suggesting its potential as an effective agent for treating osteoclast-induced osteoporosis.
Osteoporosis is a metabolic bone-loss disease characterized by abnormally excessive osteoclast formation and bone resorption. Identification of natural medicines that can inhibit osteoclastogenesis, bone resorption, and receptor activator of nuclear factor-kappa B ligand (RANKL)-induced signaling is necessary for improved treatment of osteoporosis. In this study, hinokitiol, a tropolone-related compound extracted from the heart wood of several cupressaceous plants, was found to inhibit RANKL-induced osteoclast formation and bone resorption in vitro. Hinokitiol inhibited early activation of the ERK, p38, and JNK-MAPK pathways, thereby suppressing the activity and expression of downstream factors (c-Jun, c-Fos, and NFATC1). Consistent with the above in vitro findings, hinokitiol treatment protected against ovariectomy-induced bone loss in vivo. Collectively, our results imply that hinokitiol can potentially serve as an effective agent for treating osteoclast-induced osteoporosis.
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