Itga11 promotes osteogenic differentiation, inhibits angiogenesis and proliferation of mesenchymal stem cells under hypoxia.

Objective: This study aimed to explore the role and mechanism of hypoxic environment in rat bone mesenchymal stem cells (rBMSCs) proliferation, osteogenic differentiation and angiogenesis.

Methods: Cell proliferation, angiogenesis and osteogenic differentiation were assessed using the CCK-8 assay, tube formation assay and alizarin red staining, respectively. Transcriptomic databases for rBMSCs under hypoxic (1 % O) and normoxic (18 % O) conditions were constructed to identify differentially expressed genes (DEGs), which were then subjected to gene function annotation and KEGG pathway analysis. To modulate the expression of Itga11, siRNA targeting Itga11 (si-Itga11) and a negative control (si-con), as well as pcDNA-Itga11 and an empty control plasmid (pcDNA), were employed to induce silencing or overexpression of Itga11. The protein levels were evaluated using Western blot analysis.

Results: Hypoxia stimulated the proliferation and angiogenesis of rBMSCs but suppressed their osteogenic differentiation. Differential expression analysis identified 541 upregulated and 277 downregulated genes in the hypoxic group compared to the normoxic group. KEGG pathway enrichment analysis suggested that the hypoxic response in rBMSCs is closely associated with the Pi3k /Akt signaling pathway. Itga11 was significantly downregulated in rBMSCs under hypoxic conditions. Overexpression of Itga11 in rBMSCs inhibited their proliferation and angiogenesis and enhanced osteogenic differentiation, while its knockdown had the opposite effect. Itga11 was found to activate the Pi3k /Akt signaling pathway in rBMSCs.

Conclusion: Itga11 facilitates osteogenic differentiation and suppresses angiogenesis and proliferation of MSCs under hypoxia by activating the Pi3k /Akt signaling pathway.