Abstract
BackgroundIntegrins play a prominent role in osteogenic differentiation by transmitting both mechanical and chemical signals. Integrin expression is closely associated with tensile stress, which has a positive effect on osteogenic differentiation. We investigated the relationship between integrin αVβ3 and tensile stress.MethodsHuman fibroblasts were treated with c (RGDyk) and lentivirus transduction to inhibit function of integrin αVβ3. Y-15, cytochalasin D and verteporfin were used to inhibit phosphorylation of FAK, polymerization of microfilament and function of nuclear YAP, respectively. Fibroblasts were exposed to a cyclic tensile stress of 10% at 0.5 Hz, once a day for 2 h each application. Fibroblasts were harvested on day 4 and 7 post-treatment. The expression of ALP, RUNX2, integrin αVβ3, β-actin, talin-1, FAK, vinculin, and nuclear YAP was detected by Western blot or qRT-PCR. The expression and distribution of integrin αVβ3, vinculin, microfilament and nuclear YAP.ResultsCyclic tensile stress was found to promote expression of ALP and RUNX2. Inhibition of integrin αVβ3 activation downregulated the rearrangement of microfilament and the expression of ALP, RUNX2 and nuclear YAP. When the polymerization of microfilament was inhibited the expression of ALP, RUNX2 and nuclear YAP were decreased. The phosphorylation of FAK induced by cyclic tensile stress reduced by the inhibition of integrin αVβ3. The expression of ALP and RUNX2 was decreased by inhibition of phosphorylation of FAK and inhibition of nuclear YAP.ConclusionsCyclic tensile stress promotes osteogenesis of human fibroblasts via integrin αVβ3-microfilament axis. Phosphorylation of FAK and nuclear YAP participates in this process.
Highlights
Large bone defects, whether caused by trauma, tumors, or infection, require external bone repair
We investigated the relationship between integrin αVβ3 and early stage of osteogenic differentiation induced by cyclic tensile stress (CTS)
We found that focal adhesion kinase (FAK) participated in the formation of focal adhesions, and phosphorylation of FAK mediated by integrin αVβ3 played a role in early stage of osteogenic differentiation induced by CTS
Summary
Large bone defects (with a fracture space > 2.5 cm), whether caused by trauma, tumors, or infection, require external bone repair. Fibroblasts and mesenchymal stem cells have similar MSC markers and can differentiate into cells of osteogenic, adipogenic, and chondrogenic lineages [7, 8]. Peng et al Stem Cell Res Ther (2021) 12:523 patients show an enhanced potential for osteogenic differentiation in agreement with the heterotopic ossification characterizing this disease [9]. In another approach, the subcutaneous ectopic bone formation in mice after implantation of the epigenetically modified fibroblasts [10]. Clinical and basic studies have shown that external mechanical stimulation, such as increased tension in response to stretch, can affect osteogenic differentiation of stem cells [15, 16]. We investigated the relationship between integrin αVβ3 and tensile stress
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