RETRACTED ARTICLE: Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis

• Published in: Cell death & disease Vol. 8; no. 9; p. e3037
• Main Authors: Chen, Xiao, Zhi, Xin, Cao, Liehu, Weng, Weizong, Pan, Panpan, Hu, Honggang, Liu, Chao, Zhao, Qingjie, Zhou, Qirong, Cui, Jin, Su, Jiacan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.09.2017; Springer Nature B.V
• Subjects: 13/1; 38/77; 631/136/818; 631/443/319/1642/316/801; 631/45/612/1249; 631/80/86; 64/60; Antibodies; Biochemistry; Cell Biology; Cell Culture; Immunology; Life Sciences; original-article
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2017.394

Postmenopausal osteoporosis (POMP) is a public health problem characterized by decreased bone density and increased fracture risk. Over-activated osteoclastogenesis plays a vital role in POMP. Here we developed a novel bioactive compound MASM (M19) based on sophocarpine. Although it showed no significant effects on osteogenesis and adipogenesis for bone marrow-derived mesenchymal stem cells (BMSCs) in vitro , it could significantly inhibit RANKL/M-CSF induced osteoclastogenesis through suppressing NF- κ B, MAPKs and PI3K/Akt pathways in vitro and ameliorate bone loss in ovariectomized mice in vivo . Ribosomal protein s5 (RPS5) has been identified as a target of M19 and regulates PI3K/Akt, NF- κ B and MAPKs pathways in osteoclastogenesis. Overexpressions of RPS5 synergistically inhibited osteoclastogenesis with M19 while silencing RPS5 compromised M19 inhibitory effects on osteoclastogenesis in vitro . Among the three pathways, Akt plays a major role in M19 effects. The Akt activator SC 79 partially reversed the inhibitory effects on osteoclastogenesis by M19 and RPS5-knocking-down. It indicates that RPS5 serves as a potential candidate target for inhibiting osteoclastogenesis and osteoporosis therapy and M19 is a promising agent for POMP treatment.