CircFOXP1/FOXP1 promotes osteogenic differentiation in adipose-derived mesenchymal stem cells and bone regeneration in osteoporosis via miR-33a-5p.

Osteoporosis (OP) is defined by bone mass loss and structural bone deterioration. Currently, there are no effective therapies for OP treatment. Circular RNAs (circRNAs) have been reported to have an important function in stem cell osteogenesis and to be associated with OP. Most circRNA roles in OP remain unclear. In the present study, we employed circRNA microarray to investigate circRNA expression patterns in OP and non-OP patient bone tissues. The circRNA-miRNA-mRNA interaction was predicted using bioinformatic analysis and confirmed by RNA FISH, RIP and dual-luciferase reporter assays. ARS and ALP staining was used to detect the degree of osteogenic differentiation in human adipose-derived mesenchymal stem cells (hASCs) in vitro. In vivo osteogenesis in hASCs encapsulated in collagen-based hydrogels was tested with heterotopic bone formation assay in nude mice. Our research found that circFOXP1 was significantly down-regulated in OP patient bone tissues and functioned like a miRNA sponge targeting miR-33a-5p to increase FOXP1 expression. In vivo and in vitro analyses showed that circFOXP1 enhances hASC osteogenesis by sponging miR-33a-5p. Conversely, miR-33a-5p inhibits osteogenesis by targeting FOXP1 3'-UTR and down-regulating FOXP1 expression. These results determined that circFOXP1 binding to miR-33a-5p promotes hASC osteogenic differentiation by targeting FOXP1. Therefore, circFOXP7ay prevent OP and can be used as a candidate OP therapeutic target.

Shen W ，Sun B ，Zhou C ，Ming W ，Zhang S ，Wu X ... -  《-》

Circ_0019693 promotes osteogenic differentiation of bone marrow mesenchymal stem cell and enhances osteogenesis-coupled angiogenesis via regulating microRNA-942-5p-targeted purkinje cell protein 4 in the development of osteoporosis.

He W ，Shi X ，Guo Z ，Wang H ，Kang M ，Lv Z ... -  《-》

CircRNA-23525 regulates osteogenic differentiation of adipose-derived mesenchymal stem cells via miR-30a-3p.

Guo Z ，Zhao L ，Ji S ，Long T ，Huang Y ，Ju R ，Tang W ，Tian W ，Long J ... -  《-》

CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis.

Osteoporosis (OP), characterized by compromised bone integrity and increased fracture risk, poses a significant health challenge. Circular RNAs (circRNAs) have emerged as crucial regulators in various pathophysiological processes, prompting investigation into their role in osteoporosis. This study aimed to elucidate the involvement of circCOX6A1 in OP progression and understand its underlying molecular mechanisms. The primary objective was to explore the impact of circCOX6A1 on bone marrow-derived mesenchymal stem cells (BMSCs) and its potential interactions with miR-512-3p and DYRK2. GSE161361 microarray analysis was employed to assess circCOX6A1 expression in OP patients. We utilized in vitro and in vivo models, including BMSC cultures, osteogenic differentiation assays, and an OVX-induced mouse model of OP. Molecular techniques such as quantitative RT-PCR, western blotting, and functional assays like alizarin red staining (ARS) were employed to evaluate circCOX6A1 effects on BMSC proliferation, apoptosis, and osteogenic differentiation. The interaction between circCOX6A1, miR-512-3p, and DYRK2 was investigated through dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays. CircCOX6A1 was found to be upregulated in osteoporosis patients, and its expression inversely correlated with osteogenic differentiation of BMSCs. CircCOX6A1 knockdown enhanced osteogenic differentiation, as evidenced by increased mineralized nodule formation and upregulation of osteogenic markers. In vivo, circCOX6A1 knockdown ameliorated osteoporosis progression in OVX mice. Mechanistically, circCOX6A1 acted as a sponge for miR-512-3p, subsequently regulating DYRK2 expression. This study provides compelling evidence for the role of circCOX6A1 in osteoporosis pathogenesis. CircCOX6A1 negatively regulates BMSC osteogenic differentiation through the miR-512-3p/DYRK2 axis, suggesting its potential as a therapeutic target for mitigating OP progression.

He D ，Zheng S ，Cao J ，Deng J ，Ding R ，Xu Y ，Cheng X ... -  《-》

Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis.

Liu C ，Liu AS ，Zhong D ，Wang CG ，Yu M ，Zhang HW ，Xiao H ，Liu JH ，Zhang J ，Yin K ... -  《Cell Death & Disease》