Tendon-derived extracellular matrix induces mesenchymal stem cell tenogenesis via an integrin/transforming growth factor-β crosstalk-mediated mechanism.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA-free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor-β (TGF-β) mediated tenogenesis in human adipose-derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM-driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF-β/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis-associated markers. tECM also induced higher expression of several integrin subunits and TGF-β receptors, and nuclear translocation of p-SMAD2 in hASCs. Pharmacological inhibition of integrin-ECM binding, focal adhesion kinase (FAK) signaling, or TGF-β signaling independently led to compromised pro-tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM-driven TGFBR2 expression, while inhibiting TGF-β signaling decreased tECM-mediated expression of integrin α1, α2, and β1 in hASCs. Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-β signaling crosstalk. Understanding how integrins interact with signaling by TGF-β and/or other grow

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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