MicroRNA‐497 elevation or LRG1 knockdown promotes osteoblast proliferation and collagen synthesis in osteoporosis via TGF‐β1/Smads signalling pathway

• Published in: Journal of cellular and molecular medicine 2020-11, Vol.24 (21), p.12619-12632
• Main Authors: Gu, ZhengTao, Xie, DengHui, Huang, CaiQiang, Ding, Rui, Zhang, RongKai, Li, QingChu, Lin, ChuangXin, Qiu, YiYan
• Format: Article
• Language: English
• Subjects: Abdomen; Alcohol use; Alkaline Phosphatase - metabolism; Angiogenesis; Animal models; Animals; Apoptosis; Bioengineering; Biomarkers - metabolism; Bone density; Calcium - blood; Calcium - urine; Cell division; Cell Survival; Collagen; Collagen (type I); Collagen - biosynthesis; collagen synthesis; Down-Regulation - genetics; Enzymes; Female; Femur; Femur Head - pathology; Fractures; Gene expression; Gene Expression Regulation; Gene Knockdown Techniques; Glycoproteins - genetics; Glycoproteins - metabolism; Hydroxyproline - metabolism; Laboratory animals; Leucine; leucine‐rich alpha‐2‐glycoprotein‐1; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; microRNA‐497; miRNA; Models, Biological; Morphology; Original; osteoblast; Osteoblasts; Osteoblasts - metabolism; Osteoblasts - pathology; Osteoporosis; Osteoporosis - metabolism; Osteoporosis - pathology; Ovariectomy; Oxidative Stress; Phosphatase; Phosphorus - blood; Phosphorus - urine; Plasmids; Rats, Sprague-Dawley; Signal Transduction; Smad Proteins - metabolism; Software; Transforming Growth Factor beta1 - metabolism; transforming growth factor β1/Smads signalling pathway; Transforming growth factor-b1; Up-Regulation - genetics; viability
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15826

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‐β1)/Smads signalling pathway in osteoporosis. Thereafter, the study is set out to delve into miR‐497/LRG1/TGF‐β1/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‐β1/Smads signalling pathway‐related factors were detected. MiR‐497 was poorly expressed while LRG1 was highly expressed and TGF‐β1/Smads signalling pathway activation was inhibited in osteoporosis. MiR‐497 up‐regulation or LRG1 down‐regulation activated TGF‐β1/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‐β1/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‐β1/Smads signalling pathway, which may provide a novel reference for osteoporosis treatment.