MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

Abstract

Background: It is reported that miR-596 has a potential diagnostic value for non-traumatic osteonecrosis of the femoral head (NOFH), but its underlying mechanisms in NOFH is unclear. Methods: The expression of miR-596 and Smad3 was detected by western blot and quantitative real-time PCR. The relationship between the two molecules was explored using Dual-Luciferase Reporter Assay. Glucocorticoid (GC)dexamethasone, was used to induce bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, and the effects of miR-596 on BMSC osteogenic differentiation and proliferation were determined.Results: MiR-596 expression was upregulated, while Smad3 expression was inhibited in the bone marrow samples of patients with steroid-induced osteonecrosis of femoral head (SANFH). Overexpression of miR-596 inhibited the proliferation and osteogenic differentiation of BMSCs induced by GC. Meanwhile, the opposite results were observed in the miR-596 inhibitor group. In addition, Smad3 was a target gene of miR-596, and negatively regulated by miR-596. The promotion effect of the miR-596 inhibitor on BMSC proliferation and osteogenic differentiation was reversed by si-Smad3.Conclusion: MiR-596 can suppress GC-BMSC osteoblastic differentiation and proliferation by regulating Smad3 expression.

MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5

“…The findings revealed that miR-338-3p showed an opposite trend of expression in BMSCs with age and exerted negative functions on PCSK5, thereby limiting bone formation. Several studies also reported that an increasing number of miRNAs could regulate BMSC differentiation ( 31 – 33 ). In the present study, increased expression of miR-338-3p was observed in BMSCs of older rat samples, which indicated a counter-productive role of miR-338-3p in osteogenesis.…”

MiR-423-5p downregulates osteoblastic differentiation and cell viability by targeting SMAD3 in non-traumatic osteonecrosis

“…Previous studies have disclosed that abnormal MSC differentiation leads to reduced osteogenic differentiation in ONFH patients [6]. In addition, accumulated evidence has demonstrated that many miRNAs, including miR-17-5p [9], miR-186-5p [10], miR-217 [11], and miR-596 [15] are involved in MSC differentiation in ONFH patients. In the current study, miR-423-5p levels were significantly increased in ONFH samples or during osteoblastic differentiation.…”

Beware of Steroid-Induced Avascular Necrosis of the Femoral Head in the Treatment of COVID-19—Experience and Lessons from the SARS Epidemic

“… 15 Fu et al found that the expression of microRNA 596 ( miR-596) in the bone marrow of patients with steroid-induced femoral head necrosis (FHN) was upregulated, which could hinder the repair of the osteonecrotic bone by inhibiting the proliferation and osteogenic differentiation of the bone marrow stromal cells (BMSCs). 16 Some basic studies have found that microRNA-17-5p ( miR-17-5p ) and miR-210 are related to the pathogenesis of SANFH. 17 , 18 Du et al confirmed for the first time that four sensitive single-nucleotide polymorphisms (SNPs), namely, rs3740938, rs2012390, rs1940475, and rs11225395 of MMP8 from the MMP (matrix metalloproteinases)/TIMP (tissue inhibitors of MMP) system were significantly correlated with the increased risk of steroid-induced FHN in a study conducted in northern China.…”