1. Academic Validation
  2. Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity

Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity

  • Biochem Pharmacol. 2020 Jan;171:113715. doi: 10.1016/j.bcp.2019.113715.
Jiahong Meng 1 Wenkan Zhang 1 Cong Wang 1 Wei Zhang 2 Chenhe Zhou 1 Guangyao Jiang 1 Jianqiao Hong 1 Shigui Yan 3 Weiqi Yan 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Orthopedic Research Institute of Zhejiang University, Hangzhou, China.
  • 2 Department of Burns & Wound Care Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Orthopedic Research Institute of Zhejiang University, Hangzhou, China. Electronic address: zrjwsj@zju.edu.cn.
  • 4 Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Orthopedic Research Institute of Zhejiang University, Hangzhou, China. Electronic address: wyan@zju.edu.cn.
Abstract

Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects. However, its effects on osteoclast formation and function remain unknown. In the present study, we showed that catalpol inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, as well as the expression of osteoclast-related marker genes. The investigation of molecular mechanisms showed that catalpol upregulated Phosphatase and tensin homolog (PTEN) activity by reducing its ubiquitination and degradation, subsequently suppressing RANKL-induced NF-κB and Akt signaling pathways, leading to an inhibition on NFATc1 induction. Furthermore, catalpol protected mice against inflammation- and ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo. These results suggest that catalpol might be developed as a promising candidate for treating osteoclast-related bone diseases.

Keywords

Catalpol; Catalpol (PubChem CID91520); Cycloheximide (PubChem CID6197); Inflammation; NFATc1; Osteoclast; Osteoporosis; PTEN; VO-Ohpic (PubChem CID90488861).

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