Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice |
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| Institution: | 1. Key laboratory of Zoonosis, Ministry of Education, Central Laboratory, The second clinical hospital,Jilin University, Changchun, 130041, PR China;2. School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China;3. College of chemistry and biology, Beihua University, Jilin 132013, PR China;1. Department of Neurology, The Affiliated Hospital of the Qingdao University, Qingdao, Shandong Province 266003, PR China;2. Central Laboratory, The Affiliated Hospital of the Qingdao University, Qingdao, Shandong Province 266003, PR China;3. Laboratory of Human Micromorphology, The Medical College of Qingdao University, Qingdao 266003, PR China;1. Division of Molecular Regulation, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan;2. Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;3. Laboratory of Pharmacology, Faculty of Pharmaceutical Science, Aomori University, 2-3-1 Koubata, Aomori 030-0943, Japan;4. Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan;5. Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan;6. Division of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan;7. Department of Pediatric Dentistry, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan;8. Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 48-1955, Japan;1. Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, China;2. Department of Radiotherapy, First Affiliated Hospital, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, China |
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| 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. |
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