Role of integrin β1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel
© The Author(s) 2024. Published by Oxford University Press..
Cartilage defects may lead to severe degenerative joint diseases. Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair. However, the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified. Herein, we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis. Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-β signaling pathway, and integrin-β1 (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 group. Knockdown of ITGB1 led to the downregulation of cartilage-specific genes (SOX9, ACAN, COL2A1), SMAD2 and TNC, as well as the downregulation of phosphorylation of SMAD2/3. Knockdown of TNC also resulted in the decrease of cartilage markers, ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend. Finally, in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration. In summary, we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel. It 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 chondrogenesis. These may provide concernful support for cartilage tissue engineering and biomaterials development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Regenerative biomaterials - 11(2024) vom: 20., Seite rbae017 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Yuanjun [VerfasserIn] |
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| Links: |
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| Themen: |
Chondrogenic induction |
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| Anmerkungen: |
Date Revised 26.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1093/rb/rbae017 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370148959 |
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| 520 | |a © The Author(s) 2024. Published by Oxford University Press. | ||
| 520 | |a Cartilage defects may lead to severe degenerative joint diseases. Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair. However, the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified. Herein, we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis. Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-β signaling pathway, and integrin-β1 (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 group. Knockdown of ITGB1 led to the downregulation of cartilage-specific genes (SOX9, ACAN, COL2A1), SMAD2 and TNC, as well as the downregulation of phosphorylation of SMAD2/3. Knockdown of TNC also resulted in the decrease of cartilage markers, ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend. Finally, in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration. In summary, we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel. It 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 chondrogenesis. These may provide concernful support for cartilage tissue engineering and biomaterials development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a TGF-SMAD2/3 signaling | |
| 650 | 4 | |a chondrogenic induction | |
| 650 | 4 | |a collagen hydrogel | |
| 650 | 4 | |a integrin β1 | |
| 650 | 4 | |a tenascin C | |
| 700 | 1 | |a Sun, Miao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Zhenhui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Qiuling |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Manli |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Qingjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Li |e verfasserin |4 aut | |
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