CircRUNX2 through has‐miR‐203 regulates RUNX2 to prevent osteoporosis

Abstract

ObjectiveWe aimed to discover the molecular mechanism of hsa_circ_0076694 (circRUNX2) on osteogenic differentiation. We also explored the interaction between circRUNX2, miR‐203 and RUNX2.MethodsClinical samples obtained from femoral neck fracture patients’ bone tissues were used to collect circRUNX2, miR‐203, and RUNX2 expression data, while their expression changes were observed in human bone mesenchymal stem cells (hBMSCs) during osteogenic differentiation. QRT‐PCR and Western blot were used to analyse levels of RNAs and proteins. Biotin pull down, RIP, RNA FISH, and Dual‐Luciferase Reporter assays demonstrated the relationship between circRUNX2, miR‐203, and RUNX2. ALP and ARS staining were used to measure the degree of osteogenic differentiation under the control of circRUNX2, miR‐203.ResultsCircRUNX2 were down‐regulated in osteoporotic patients’ bone tissues. CircRUNX2 could inhibit miR‐203 expression by sponging miR‐203. MiR‐203 inhibited osteogenic differentiation by targeting the 3′‐UTR of RUNX2 and down‐regulate RUNX2 expression. Overexpression of circRUNX2 promoted the expression of osteogenic differentiation‐related proteins such as RUNX2, OCN, OPN, BSP, and prevented osteoporosis.ConclusioncircRUNX2 could sponge miR‐203 and enhance RUNX2 expression, thus circRUNX2 prevents osteoporosis and may provide a novel therapeutic strategy for it.

Chondroitin Sulfate Prevents STZ Induced Diabetic Osteoporosis through Decreasing Blood Glucose, AntiOxidative Stress, Anti-Inflammation and OPG/RANKL Expression Regulation

“…RUNX2 is a bone specific transcription factor. It is an important sign of osteoblasts differentiation and the process of bone formation [38]. High expression of RUNX2 can activate the transcription of bone sialoprotein (BSP) and osteocalcin, thereby promoting the maturation of osteoblasts and bone formation [39].…”

Activation of GPR30 promotes osteogenic differentiation of MC3T3‐E1 cells: An implication in osteoporosis

“…For example, one study showed that Runx2 might increase the responsiveness of osteogenic cells to mitogenic signals by activating GPR30 . Another more recent study demonstrated that antagonism of GPR30 hindered the mineralization of MC3T3‐E1 cells induced by psoralidin, a common osteoporosis treatment agent . Concordantly, our findings show that agonism of GPR30 by G1 significantly upregulated expression of Runx2, and in turn, increased osteoblastic differentiation of MC3T3‐E1 cells.…”

Identification and Comparison of Novel Circular RNAs With Associated Co-expression and Competing Endogenous Rna Networks in Postmenopausal Osteoporosis

“…Similarly, highly expressed circ-SFMBT2 was observed in gastric cancer tissues, and proved to participate in the pathogenesis of gastric cancer via sponging miR-182-5p [22]. To date, only a few pathogenic circRNAs were reported in osteoporosis, and RNA sequencing tools and bioinformatics analysis were not employed in these studies [23][24][25]. Here, we constructed ceRNA networks with differentially expressed circRNAs and mRNA from whole transcriptome sequencing data, as well as intermediate miRNAs predicted through bioinformatics analysis.…”