Involvement of circRNA_0007059 in the regulation of postmenopausal osteoporosis by promoting the microRNA‐378/BMP‐2 axis

Abstract

Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA‐seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP‐2) expression, upregulated osteoclast‐specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR‐378, which in turn targeted BMP‐2 via bioinformatics analysis and the dual‐luciferase reporter assay. Transfection of the miR‐378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR‐378/BMP‐2 signaling pathway. Targeting the circ_0007059/miR‐378/BMP‐2 axis is possibly a novel idea in osteoporosis treatment.

MicroRNA-151a-3p Functions in the Regulation of Osteoclast Differentiation: Significance to Postmenopausal Osteoporosis

“…39 Previous studies have found that miR-93-5p and miR-378 were involved in the regulation of OP by binding to BMP-2, a number of active bone morphogenetic proteins. 46,47 Therefore, BMP-2 may play a critical role in miRNA-mediated regulation of OP.…”

“… 39 Previous studies have found that miR-93-5p and miR-378 were involved in the regulation of OP by binding to BMP-2, a number of active bone morphogenetic proteins. 46 , 47 Therefore, BMP-2 may play a critical role in miRNA-mediated regulation of OP. In our future study, we will further investigate whether microRNA-151a-3p functions in OP by directly binding to BMP-2.…”

Role of Biomolecules in Osteoclasts and Their Therapeutic Potential for Osteoporosis

“…Another study reported that during osteoclast differentiation, the level of circRNA_009934 was also increased, and circRNA_009934 functioned as a ceRNA of miR-5107 to promote osteoclastogenesis [ 102 ]. Conversely, the overexpression of circ_0007059 reduced hBMSC differentiation into osteoclasts and bone morphogenetic protein 2 (BMP-2) in vitro by directly targeting miR-378 [ 103 ]. Liu et al have demonstrated that circHmbox1 could also suppress RANKL-induced osteoclasts differentiation by binding to miR-1247-5p [ 104 ].…”

Circular RNAs in osteoporosis: expression, functions and roles

“…Large numbers of circRNAs have been shown to play crucial roles in osteoporosis. For example, by studying 40 women with PMO (postmenopausal osteoporosis), Liu et al discovered that circZNF720 (circbase ID: circ_0007059) could attenuate osteoclast differentiation through the microRNA-378/BMP2 axis, which in turn repressed osteoporosis [ 22 ]. circPRIM2 (circbase ID: hsa_circ_0076906) binds to miR-1305 to regulate the expression of OGN (osteoglycin) and alleviate osteoporosis [ 23 ].…”

“…Among 40 women with PMO (postmenopausal osteoporosis) and paired normal controls, Liu et al selected five samples for RNA sequencing, which showed that 250 differentially expressed circRNAs were present in osteoporosis, 64 circRNAs showed a decreasing expression trend, and 186 other circRNAs were increased (filtration criteria: |fold alternation | > 2 and P < 0.01). Among the six top circRNAs with different expression levels (circ_0043813, circ_0001649, and circ_0005654 were upregulated, circ_0007059, circ_0001204, and circ_0001795 were downregulated), Liu et al chose to examine circ_0007059 in osteoporotic samples and discovered that circ_0007059 expression was reduced in osteoporotic samples [ 22 ].…”