Knockdown of SERPINB2 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signalling pathway [post]

Kai Hang, Li Ying, Jinwu Bai, Yibo Wang, Zhihui Kuang, Dating Xue, Zhijun Pan
2021 unpublished
Background Globally, bone fractures are the most common musculoskeletal trauma, and approximately 8–10% of cases that fall into the categories of delayed or non-union healing. Treatment of impaired healing in these patients not only represents a tremendous burden on healthcare systems but also increases patients' pain and financial burdens. To date, there are no efficient pharmacological agents to accelerate the healing of bone fractures. Thus, it is necessary to find new strategies that
more » ... ate bone healing and reduce the incidence of non-union or delayed fracture healing. Previous studies have revealed that the plasminogen activation system has been demonstrated to play an important role in bone metabolism. However, the function of SERPINB2 in the osteogenesis of hBMSCs remains unclear. Therefore, in this study, we investigated the effects and mechanism of Apelin on osteogenic differentiation. Methods We investigated the osteogenesis effects of hBMSCs by both exogenous SERPINB2 protein and SERPINB2 silencing in vitro. Cell proliferation assay was used to assess the effect of exogenous SERPINB2 or SERPINB2 silencing on proliferation of hBMSCs. qPCR and Western blotting analysis detected the expression of target genes and proteins respectively. ALP staining was used to evaluated ALP activity and Alizarin Red staining (ARS) was used to evaluate mineral deposition. In vivo, a murie tibial fracture model was established, histological evaluation and radiographic analysis was used to confirm the therapeutic effects of SERPINB2 silencing in fracture healing. statistical significance between two groups was determined by Student's t test, one-way ANOVA or Bonferroni's post-hoc test according to the distribution of the tested population.Results The addition of exogenous SERPINB2 protein inhibted osteoblast differentiation of hBMSCs in vitro, while SERPINB2 gene silencing significant promote osteoblast differentiation of hBMSCs in vitro. And silence SERPINB2 gene also increased mineral deposits. Moreover, β-catenin levels were up-regulated by SERPINB2 gene depletion. And the enhancement of osteogenic differentiation induced by SERPINB2 silencing was almost inhibited by specific Wnt/β-catenin signaling pathway inhibitors. In a murine tibial fracture model, local injection of SERPINB2 siRNA improved bone fracture healing. Conclusions Taken together, these findings indicate that SERPINB2 silencing promoted osteogenic differentiation of BMSCs via the Wnt/β-catenin signaling pathway, and silenced SERPINB2 in vivo effectively promotes fracture healing, suggesting that SERPINB2 may be a novel target for bone fracture healing.
doi:10.21203/ fatcat:c7b27rpr65cgnhq43xtmmmxhnq