2. Academic Validation
  3. Anethole inhibits RANKL-induced osteoclastogenesis by downregulating ERK/AKT signaling and prevents ovariectomy-induced bone loss in vivo

Anethole inhibits RANKL-induced osteoclastogenesis by downregulating ERK/AKT signaling and prevents ovariectomy-induced bone loss in vivo

  • Int Immunopharmacol. 2021 Nov;100:108113. doi: 10.1016/j.intimp.2021.108113.
Hao Qu 1,  Yuankang Zhang 2,  Rongxin He 3,  Nong Lin 4,  Cong Wang 5
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China. Electronic address: email@zju.edu.cn.
  • 2 Department of Orthopedics, XinJian District People's Hospital of Nanchang, Nanchang City, Jiangxi Province, China. Electronic address: zyk20080058@163.com.
  • 3 Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China. Electronic address: herongxin@zju.edu.cn.
  • 4 Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China. Electronic address: linnong@zju.edu.cn.
  • 5 Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China. Electronic address: 05wangcong@zju.edu.cn.
PMID: 34530203 DOI: 10.1016/j.intimp.2021.108113
Abstract

Postmenopausal osteoporosis is a chronic population health hazard systemic Metabolic Disease caused by excessive bone resorption and reduced bone formation. The activity between osteoblast and osteoclast, with their mutual effects, influence the procedure of normal bone remodeling. Over-activated osteoclast differentiation and function play a crucial role in excessive bone resorption. Hence, therapy strategies targeting osteoclast activity may promote the bone mass preservation and delay the osteoporosis process. Natural compound (anethole) is emerging as potential therapeutics for various metabolic diseases. The purpose of this study is to investigate the potential effects of anethole on RANKL-induced osteoclast formation and function in vitro and in vivo. Here, in vitro TRAP staining assay was performed to investigate the inhibitory effect of anethole on osteoclast differentiation. Bone pits resorption assay revealed that osteoclast-mediated bone resorption was inhibited by anethole. At mRNA and protein levels, anethole significantly reduced the expression of osteoclast-specific genes expression in a concentration- or time-dependent manner, including NFATc1, MMP-9, DC-STAMP, c-F, TRAP, CTR, Cathepsin K, and V-ATPase d2. Furthermore, intracellular signaling transduction assay indicated that anethole inhibited osteoclast formation via blocking ERK and Akt signaling. GSK3β, the downstream signal of Akt, is simultaneously suppressed with anethole treatment. Based on ovariectomized (OVX) mice model, micro-CT and histological staining results suggested that anethole prevented estrogen deficiency-induced bone mass loss and increased osteoclast activity in vivo. In conclusion, our results show significant indications that anethole exhibits an osteoprotective effect and may be potential for the treatment of osteoporosis.

Keywords

Anethole; NFATc1; Osteoclast; Osteoporosis; RANKL.

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