Abstract
BackgroundMultiple microRNAs (miRNAs) have been proven to regulate osteogenic differentiation by affecting the Runx2 signaling pathway. The intervention of miRNA can delay the progress of osteoporosis (OP) and induce fracture repair by affecting bone regeneration. However, the function and mechanism of miR-187 in osteoporotic fractures are still unknown. MethodsWe first established the OP mouse model. Next, the BMD value was certified by iDXA. The miR-187 level in the OP mice and serum of OP patients was identified through qRT-PCR. Bone repair and bone healing were assessed through toluidine blue staining and X-ray, and BARX2 expression was also confirmed. Osteogenesis-related proteins, ALP activity, and the matrix mineralization state were evaluated by western blot, ALP staining, and Alizarin Red staining in hMSCs after transfection with miR-187 mimics, miR-187 inhibitor, or human BarH-like homeobox 2 (BARX2) siRNA. Moreover, the interplay between miR-187 and BARX2 was identified through the dual-luciferase reporter. ResultsThe BMD value was notably reduced in the OP mice, and miR-187 was markedly downregulated in the OP mice and serum of OP patients. Meanwhile, we proved that miR-187 induced bone reconstruction and healing, and downregulated BARX2 in the OP mouse model. We also proved that BARX2 was a direct target of miR-187, and could be significantly downregulated by miR-187. Furthermore, miR-187 induced osteogenic differentiation of hMSCs by targeting BARX2. ConclusionsThe miR-187 might have a significant therapeutic effect in osteoporotic fractures. miR-187 accelerated osteogenic differentiation of hMSCs by directly regulating BARX2.
Highlights
Multiple microRNAs have been proven to regulate osteogenic differentiation by affecting the Runx2 signaling pathway
Osteoporosis is characterized by reduced bone mass, decreased bone mineral density, and destruction of bone microstructure, which can result in increased bone fragility, and even an increased risk of fracture [3, 4]
We further investigated the expression of miR-187 in the OP mouse model and the serum of osteoporosis patients
Summary
Multiple microRNAs (miRNAs) have been proven to regulate osteogenic differentiation by affecting the Runx signaling pathway. The intervention of miRNA can delay the progress of osteoporosis (OP) and induce fracture repair by affecting bone regeneration. Osteoporosis (OP) is a universal metabolic bone disease and has been recognized as a major public health problem worldwide [1]. Osteoporotic fractures have become the most serious complication of osteoporosis [5]. OP therapy drugs are broadly divided into basic drugs and anti-absorption drugs. These drugs cannot induce bone formation and have considerable side effects [10, 11]. Further studies on the molecular mechanisms of osteoporosis are crucial for therapies for osteoporosis
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