Overexpression of miR125b Promotes Osteoporosis Through miR-125b-TRAF6 Pathway in Postmenopausal Ovariectomized Rats

Abstract

Background Postmenopausal osteoporosis is one of the most common types of osteoporosis that women suffer from. Studies involving molecular mechanisms for designing better therapeutic strategies for postmenopausal osteoporosis are still rare. The present study investigates the role of miR-125b in postmenopausal osteoporosis. Methods Microarray analysis was done to screen the gene database. Tissue samples of postmenopausal women were collected to study the miRNA profiles. MC3T3-E1 cells were used and were submitted for transfection. CCK-8 assay was done to check the viability of cells, whereas toxicity was done by lactate dehydrogenase assay kit. TargetScan was done to target genes of miR-125b followed by confirmation by Luciferase reporter assay. For animal studies a rat model of ovariectomized rats was created. Bone mineral density and biomechanics were measured by densitometer. The mRNA levels were assessed by qRT-PCR and proteins by Western blot assay. Results miR-125b was over-expressed in human osteoporosis samples. In vitro studies suggested that miR-125b suppressed the cell viability and promoted release of LDH, it also enhanced the RANKL/OPG ratio and suppressed levels of BMP2 and Runx2. Bioinformatics identified TRAF6 as a potential target of miR-125b, further confirmed by luciferase assay, also miR-125b negatively regulated the levels of TRAF6 gene in osteoporosis bones involving the JAK2/STAT3 cascade. In the rat model, miR-125b decreased the bone mineral density and biomechanical parameters in bones by altering the TRAF6 gene involving the JAK2/STAT3 pathway. Conclusion The outcomes suggested that miR-125b was responsible for the development of postmenopausal osteoporosis and promoted its progression by the TRAF6 gene via the JAK2/STAT3 pathway.

Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling

“…The JAK2/STAT3 pathway is critical for osteoblast differentiation and osteoporosis development. 16 Furthermore, naringin was reported to suppress the activation of the JAK2/STAT3 pathway in the previous study. 15 Therefore, we detected the influence of naringin on the levels of proteins associated with the JAK2/ STAT3 pathway.…”

“…15 The JAK2/STAT3 pathway was shown to play a pivotal role in the initiation and development of osteoporosis. 16 Therefore, we inferred that naringin influences BMSC osteogenic differentiation to regulate the development of osteoporosis via the JAK2/STAT3 pathway.…”

STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis

“…In vitro studies suggested that miR-125b enhanced the RANKL/OPG ratio and suppressed the levels of BMP2 and Runx2 and cell viability. In a rat OVX model, miR-125b activated the JAK2/STAT3 pathway by altering the downstream target gene TRAF6, thereby reducing bone mineral density and bone biomechanical parameters [ 76 ]. Furthermore, miR‐224 may serve as a positive mediator of osteogenic differentiation by deactivating the JAK/STAT3 and Wnt/β-catenin pathways by targeting Rac1 [ 77 ] (Table 2 ; Fig.…”

Three‐dimensional starch‐based scaffold decorated with 64S bio‐glass for accelerating rat model bone defect repair

“…In their investigations, Wang et al. demonstrated that osteoporosis is encouraged by the initiation and expansion of the Janus activated kinase 2 (JAK2)/signal transducer and the activator of transcription 3 (STAT3) pathway 105 . In confirmation, it was found that naringin can cause osteogenesis through preventing the onset and development of the JAK2/STAT3 pathway 104 .…”