摘要Background:Human adipose-derived stem cells(hADSCs)are seed cells with applica-tion prospects in cartilage repair.However,the mechanism of hADSC chondrogenic differentiation is still unclear.This study identifies a novel circRNA,circNR3C2,which is significantly upregulated during the chondrogenic differentiation of hADSCs.Methods:To analyze their role in hADSC chondrogenic differentiation,hADSCs were separated and identified by flow cytometry.Thereafter,we conducted Alcian Blue staining to assess chondrogenic differentiation levels.Additionally,RT-qPCR was car-ried out to detect levels of the cartilage-related genes COL2,Aggrecan and SOX9.Moreover,overlapping target SOX9 and circNR3C2 miRNAs were detected by bioin-formatics and luciferase analyses.Finally,the role of circNR3C2 was confirmed in vivo using animal models.Results:We confirmed that the cell surface receptors CD44,CD90 and CD105 were positively expressed on hADSCs,and their cartilage differentiation levels dramati-cally increased after 2weeks.Expression of the cartilage-related genes COL2 and Aggrecan and circNR3C2 also markedly increased.CircNR3C2 overexpression en-hanced cartilage differentiation of hADSCs,while up-regulating COL2,SOX9 and Aggrecan.Bioinformatics analysis identified hsa-miR-647 as the target miRNA of circ-NR3C2 and SOX9.Hsa-miR-647 overexpression in hADSCs can antagonize the effect of circNR3C2 on chondrogenic differentiation,and reverse its effect on regulating the expression of COL2,Aggrecan,and SOX9.We also showed that hADSCs overexpress-ing circNR3C2 promote cartilage repair in vivo.Conclusions:We show that circNR3C2 modulates SOX9 expression to promote hsa-miR-647-mediated hADSC chondrogenic differentiation;targeting circNR3C2 may help to develop new treatments to manage cartilage-related disorders.