DOI: 10.1002/ame2.12561
circNR3C2 promotes chondrogenic differentiation and cartilage repair of human adipose-derived stem cells via the hsa-miR-647/SOX9 pathway
Dabiao Hou1
Huajun Wang2
Hao Guo3
Dongbin Luo3
Xiaofei Zheng2
Simin Luo4
1.Department of Bone and Joint Surgery,The First Affiliated Hospital,Jinan University,Guangzhou,Guangdong,China;Department of Orthopedics,Guangzhou Hospital of Integrated Traditional and Western Medicine,The Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,Guangdong,China2.Department of Sports Medicine,The First Affiliated Hospital,Guangdong Provincial Key Laboratory of Speed Capability,The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine,Jinan University,Guangzhou,Guangdong,China3.Department of Orthopedics,Guangzhou Hospital of Integrated Traditional and Western Medicine,The Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,Guangdong,China4.Department of Bone and Joint Surgery,The First Affiliated Hospital,Jinan University,Guangzhou,Guangdong,China
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.
机标关键词：pathwaystemhumancellsadipose-derivedcartilagechondrogeniccircnr3c2
论文发表日期：2025-12-30
在线出版日期：2026-03-25（本平台首次上网日期，不代表文献的发表时间）
页数：13( 2209-2221 )
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