2. Academic Validation
  3. Hinokitiol inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo

Hinokitiol inhibits RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced bone loss in vivo

  • Int Immunopharmacol. 2021 Jul;96:107619. doi: 10.1016/j.intimp.2021.107619.
Yanben Wang 1,  Qichang Yang 2,  Ziyuan Fu 1,  Peng Sun 2,  Tan Zhang 3,  Kelei Wang 1,  Xinyu Li 1,  Yu Qian 4
Affiliations

Affiliations

  • 1 Department of Orthopedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, China; Department of Orthopedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China.
  • 2 Department of Orthopedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, China; The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 3 Department of Orthopedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, China.
  • 4 Department of Orthopedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, China. Electronic address: doctor120@hotmail.com.
PMID: 33831806 DOI: 10.1016/j.intimp.2021.107619
Abstract

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-κB 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.

Keywords

Hinokitiol; MAPK; NFATc1; Osteoclast; RANKL.

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