Abstract
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.
Highlights
As a chronic systemic bone disease, osteoporosis (OP) manifests as less bone mass and a disorder of bone structure, which eventually contributes to the risk of fracture [1,2]
Changes in osteoblast or osteoclast production or the life span contribute to an imbalance between bone formation and resorption, which eventually results in OP [3]
OP, a frequently occurring disease, is a metabolic bone disorder that affects millions of individuals worldwide whose high morbidity leads to a high rate of disability, extreme pain and a reduced quality of life [18,19]
Summary
As a chronic systemic bone disease, osteoporosis (OP) manifests as less bone mass and a disorder of bone structure, which eventually contributes to the risk of fracture [1,2]. Changes in osteoblast or osteoclast production or the life span contribute to an imbalance between bone formation and resorption, which eventually results in OP [3]. Alendronate (ALN) treatment is an effective anti-bone absorbent, which can promote the apoptosis of osteoclasts under the condition of extremely high doses c 2018 The Author(s). In the differentiation of bone cells, microRNAs (miRNAs) serve irreplaceable functions, regulating the lineage commitment and cell progression of mesenchymal stem cells [8]
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