Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway

• Published in: Bioscience reports 2018-12, Vol.38 (6)
• Main Authors: Pan, Bao-Long, Tong, Zong-Wu, Li, Shu-De, Wu, Ling, Liao, Jun-Long, Yang, Yu-Xi, Li, Hu-Huan, Dai, Yan-Juan, Li, Jun-E, Pan, Li
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - drug effects; Adenylyl Cyclases - genetics; Alendronate - administration & dosage; Animals; Butadienes - administration & dosage; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Proliferation - drug effects; Cell Proliferation - genetics; Gene Expression Regulation - drug effects; Humans; MAP Kinase Kinase 1 - antagonists & inhibitors; MAP Kinase Kinase 1 - genetics; MicroRNAs - genetics; Nitriles - administration & dosage; Osteoblasts - drug effects; Osteoporosis - drug therapy; Osteoporosis - genetics; Osteoporosis - pathology; Rats; Shelterin Complex; Signal Transduction - drug effects; Telomere-Binding Proteins - genetics
• ISSN: 0144-8463; 1573-4935; 1573-4935
• DOI: 10.1042/BSR20180696

Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.