RETRACTED ARTICLE: Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis

作者：Xiao Chen, Xin Zhi, Liehu Cao, Weizong Weng, Panpan Pan, Honggang Hu, Chao Liu, Qingjie Zhao, Qirong Zhou, Jin Cui, Jiacan Su · 发表于：Cell Death and Disease · 年份：2017 · DOI：10.1038/cddis.2017.394 · 被引用次数：51 · 研究领域：Bone Metabolism and Diseases、RNA Research and Splicing、Cytokine Signaling Pathways and Interactions

Abstract 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.