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Role of integrin b1 and tenascin C mediate tgf-smad2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel

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Regenerative Biomaterials 2024年第5期3卷 59-73页

作者： Yuanjun Huang Miao Sun Zhenhui Lu Qiuling Zhong Manli Tan Qingjun Wei Li Zheng Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed by the Province and Ministry First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Department of Trauma Orthopedic and Hand Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Life Science Institute Guangxi Medical UniversityNanning 530021China

Cartilage defects may lead to severe degenerative joint *** engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage ***,the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully ***,we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced *** showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the tgf-b signaling pathway,and integrin-b1(ITGB1),a receptor of collagen,was highly expressed in bone marrow mesenchymal stem cells(BMSCs).Further analysis showed genes such as COL2A1 and Tenascin C(TNC)that interacted with ITGB1 were significantly enriched in extracellular matrix(ECM)structural constituents in the chondrogenic induction *** of ITGB1 led to the downregulation of cartilage-specific genes(SOX9,ACAN,COL2A1),smad2 and TNC,as well as the downregulation of phosphorylation of smad2/*** of TNC also resulted in the decrease of cartilage markers,ITGB1 and the smad2/3 phosphorylation but overexpression of TNC showed the opposite ***,in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage *** summary,we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen *** can activate tgf-smad2/3 signaling,followed by impacting TNC expression,which in turn promotes the interaction of ITGB1 and tgf-smad2/3 signaling to enhance *** may provide concernful support for cartilage tissue engineering and biomaterials development.

关键词： collagen hydrogel chondrogenic induction integrin b1 tenascin C tgf-smad2/3 signaling

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