2. Academic Validation
  3. Catharanthine tartrate ameliorates osteoclastogenesis by destabilizing HIF-1α

Catharanthine tartrate ameliorates osteoclastogenesis by destabilizing HIF-1α

  • Cell Signal. 2025 Jul:131:111779. doi: 10.1016/j.cellsig.2025.111779.
Luqiong Cai 1,  Chenxin Yu 1,  Binli Zhao 1,  Qihang Wu 2,  Haibo Liang 2,  Meng Zhou 3,  Jiansen Miao 2,  Jiangtao Luo 2,  Jiake Xu 4,  Haiming Jin 5,  Youjin Pan 6
Affiliations

Affiliations

  • 1 Department of Endocrinology, The 2(nd) Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; The 2(nd) School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 2 Department of Orthopaedics, The 2(nd) Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; The 2(nd) School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 3 The 2(nd) School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 4 Department of Orthopaedics, The 2(nd) Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: jiake.xu@siat.ac.cn.
  • 5 Department of Orthopaedics, The 2(nd) Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; The 2(nd) School of Medicine, Wenzhou Medical University, Wenzhou, China. Electronic address: kkjinhaiming@126.com.
  • 6 Department of Endocrinology, The 2(nd) Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; The 2(nd) School of Medicine, Wenzhou Medical University, Wenzhou, China. Electronic address: panyj6190@163.com.
PMID: 40164418 DOI: 10.1016/j.cellsig.2025.111779
Abstract

With the aging population, postmenopausal osteoporosis (PMOP), clinically manifested by reduced bone density, weakened skeletal strength, and compromised skeletal microstructure, has become the most prevalent type. The decline in estrogen levels fosters oxidative stress and osteoclastogenesis, which significantly enhance the activity of osteoclasts. Current treatments prefer to adopt relevant strategies to inactivate osteoclasts but come with unavoidable side effects. In our study, Catharanthine Tartrate (CAT), a derivative of the alkaloid catharanthine found in Catharanthus roseus, promised to be an effective therapy for PMOP. CAT inhibited RANKL-induced osteoclast differentiation and bone resorption in vitro. Moreover, CAT inhibited osteoclast activity by enhancing the ubiquitination-mediated proteasomal degradation of HIF-1α, which reduced oxidative stress and subsequently suppressed osteoclast activity. The inhibitory effects of CAT on osteoclast function and oxidative stress were reversed by DMOG, a known inhibitor of HIF-1α degradation. Next, an in vivo mouse experiment using the Ovariectomized (OVX) model to induce osteoporosis indicated that CAT enhanced bone mass density, bone structure, and bone remodeling. Our findings revealed that CAT inhibits PMOP through facilitating HIF-1α ubiquitination and degradation, suggesting a promising therapeutic approach for this disorder.

Keywords

Hypoxia-inducible factor-1α; Osteoclastogenesis; Oxidative stress; Postmenopausal osteoporosis; RANKL.

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