MicroRNA-497 elevation or LRG1 knockdown promotes osteoblast proliferation and collagen synthesis in osteoporosis via TGF-ß1/Smads signalling pathway.

MicroRNAs (miRNAs) have been corroborated to engage in the process of cellular activities in osteoporosis. However, few researches have been conducted to expose the integrated role of miR-497, leucine-rich alpha-2-glycoprotein-1 (LRG1) and transforming growth factor beta 1 (TGF-ß1)/Smads signalling pathway in osteoporosis. Thereafter, the study is set out to delve into miR-497/LRG1/TGF-ß1/Smads signalling pathway axis in osteoporosis. Osteoporosis bone tissues and normal bone tissues were collected. Rat osteoporosis models were constructed via ovariectomy. Model rats were injected with restored miR-497 or depleted LRG1 to explore their roles in osteoporosis. Rat osteoblasts were extracted from osteoporosis rats and transfected with restored miR-497 or depleted LRG1 for further verification. MiR-497 and LRG1 expression in femoral head tissues and osteoblasts of osteoporosis rats were detected. TGF-ß1/Smads signalling pathway-related factors were detected. MiR-497 was poorly expressed while LRG1 was highly expressed and TGF-ß1/Smads signalling pathway activation was inhibited in osteoporosis. MiR-497 up-regulation or LRG1 down-regulation activated TGF-ß1/Smads signalling pathway, promoted collagen type 1 synthesis and suppressed oxidative stress in femoral head tissues in osteoporosis. MiR-497 restoration or LRG1 knockdown activated TGF-ß1/Smads signalling pathway, promoted viability and suppressed apoptosis of osteoblasts in osteoporosis. Our study suggests that miR-497 up-regulation or LRG1 down-regulation promotes osteoblast viability and collagen synthesis via activating TGF-ß1/Smads signalling pathway, which may provide a novel reference for osteoporosis treatment.

Orcinol glucoside facilitates the shift of MSC fate to osteoblast and prevents adipogenesis via Wnt/ß-catenin signaling pathway.

BACKGROUND: During osteoporosis, bone mesenchymal stem cells (BMSCs) lineage commitment shifts to adipocytes, causing fat accumulation and bone loss in the skeleton. Seeking drugs that could reverse the adipocyte fate determination of BMSCs is critical for osteoporosis therapy. As a traditional Chinese medicine, Rhizoma Curculiginis (Xianmao) has been used to treat bone diseases and promote bone healing, while the effective constituent of it and the underlying mechanisms are unknown. OBJECTIVES: The aim of this study is to unveil the role of orcinol glucoside (OG), one constituent of Rhizoma Curculiginis, in osteoporosis and BMSCs lineage commitment and to explore the underlying mechanisms. METHODS: Micro-CT and three-point bending test were performed to determine the effect of OG on bone structure and strength. qT-PCR and Western blot were performed to determine the expression of osteogenic or adipogenic differentiation markers in BMSCs. Mineralization in differentiated BMSCs was assessed by Alizarin Red staining, and lipid accumulation in the cells was evaluated by Oil Red O staining. All measurements were performed at least three times. RESULTS: OG prevented bone loss by stimulating bone formation and attenuating fat formation in bone. In vitro, OG promoted osteoblastic differentiation and inhibited adipogenic differentiation of BMSCs. Inhibition of Wnt/ß-catenin by ICG-001 significantly reversed the effect of OG on osteogenic and adipogenic differentiation of BMSCs. CONCLUSION: Our study demonstrated the role of OG in alleviating bone loss and fat accumulation in osteoporotic bone, therefore bringing a new therapeutic means to the treatment of osteoporosis.