1. Academic Validation
  2. Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice

Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice

  • Int Immunopharmacol. 2017 Aug;49:109-117. doi: 10.1016/j.intimp.2017.05.029.
Jinjin Cao 1 Qiang Lu 2 Ning Liu 2 Yu-Xin Zhang 2 Jing Wang 3 Maolin Zhang 2 Hong-Bing Wang 4 Wan-Chun Sun 5
Affiliations

Affiliations

  • 1 Key laboratory of Zoonosis, Ministry of Education, Central Laboratory, The second clinical hospital,Jilin University, Changchun, 130041, PR China; School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China; College of chemistry and biology, Beihua University, Jilin 132013, PR China.
  • 2 Key laboratory of Zoonosis, Ministry of Education, Central Laboratory, The second clinical hospital,Jilin University, Changchun, 130041, PR China; School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China.
  • 3 College of chemistry and biology, Beihua University, Jilin 132013, PR China.
  • 4 College of chemistry and biology, Beihua University, Jilin 132013, PR China. Electronic address: hbwang@tongji.edu.cn.
  • 5 Key laboratory of Zoonosis, Ministry of Education, Central Laboratory, The second clinical hospital,Jilin University, Changchun, 130041, PR China; School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China. Electronic address: wanchunsun@jlu.edu.cn.
Abstract

Previous studies reported that sciadopitysin (Sc), a type of biflavonoids, protects Reactive Oxygen Species (ROS)-mediated osteoblast dysfunction, but its role in osteoclastogenesis remains unclear. In this study, we observed that Sc dose-dependently suppressed RANKL-induced osteoclastogenesis and bone resorption. Our results indicated that Sc treatment strongly reduced RANKL-induced osteoclast-specific genes expression, including Cathepsin K (CTSK), tartrate-resistant Acid Phosphatase (TRAP) and MMP-9. Furthermore, Sc apparently attenuated RANKL-increased expressions of c-Fos and NFATc1. Meanwhile, Sc also strikingly inhibited the activation of NF-κB without altering the phosphorylation of MAPKs (p38, JNK and ERK1/2). Finally, our study demonstrated that Sc administration could reverse the bone loss in LPS-induced mice model. This study suggests that Sc inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting NF-κB activation and reducing the expression of c-Fos and NFATc1. Therefore, Sc might be benefit for RANKL-mediated osteolytic bone diseases.

Keywords

Bone loss; Bone resorption; NF-κB; NFATc1; Osteoclasts; RANKL.

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