RETRACTED ARTICLE: Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis

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-κB, 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-κB 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 SC79 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.

Corilagin suppresses RANKL‐induced osteoclastogenesis and inhibits oestrogen deficiency‐induced bone loss via the NF‐κB and PI3K/AKT signalling pathways

“…Our data revealed that Corilagin inhibits not only the NF‐κB but also the PI3K/AKT pathway. Moreover, some studies have identified that a novel factor named ribosomal protein S5 (RPS5) could regulate NF‐κB, MAPK and AKT signalling pathways, 49,50 which seems to be a promising target for osteoporosis treatment.…”

Shikimic Acid Inhibits Osteoclastogenesis in Vivo and in Vitro by Blocking RANK/TRAF6 Association and Suppressing NF-κB and MAPK Signaling Pathways

“…Finally, intracellular Ca 2+ is released, and NFATc1 is activated and osteoclastogenesis is promoted [5]. Previous studies demonstrated that overactive osteoclast function could also be induced by a deficiency of estrogen accompanied by increased levels of proinflammatory cytokines and RANKL after menopause [6,7].…”

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells

“…Bone resorption, mainly executed by OCs, is the initial event of skeletal development during the embryonic stage, postnatal growth, and bone remodeling, creating conditions for the neovascularization and bone formation [13]. At the same time, the involvement of EPCs in the early bone resorption activity is an important event for promoting skeletal development [8, 14].…”