School of Stomatology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030012, China.
Department of Implantation, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xi'an, 710032, China.
J Mol Histol. 2018 Aug;49(4):369-376. doi: 10.1007/s10735-018-9776-1. Epub 2018 May 17.
Bone regeneration is impaired in patients with type 2 diabetes mellitus (T2DM), which leads to non-healing after bone loss. The decreased osteogenic capacity of bone mesenchymal stem cells (BMSCs) might be a main reason. Sema3A, as a powerful protein promoting osteocyte differentiation, shows potential for bone regeneration treatment. BMSCs may be a therapeutic solution. In this study, we divided BMSCs from T2DM rats (BMSCs-D) and normal rats (BMSCs-N), identified their ability to differentiate into different cell types. Then we found decreased expression of Sema3A in BMSCs-D compared with BMSCs-N. Stimulating with Sema3A showed no influence in the proliferation or migration of BMSCs. However, Sema3A stimulation significantly increased the expression of osteogenic‑related genes, including type I collagen, alkaline phosphatase, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein and osteocalcin. Besides, the osteogenic capacity of BMSCs was also increased by Sema3A stimulation. In conclusion, we proved that exogenous Sema3A stimulation might repair the osteogenic capacity of BMSCs-D, thus providing a new strategy for restoring the impaired bone regeneration ability for T2DM patients.
骨再生在 2 型糖尿病（T2DM）患者中受损，导致骨丢失后无法愈合。骨髓间充质干细胞（BMSCs）成骨能力下降可能是主要原因。Sema3A 作为一种促进破骨细胞分化的强大蛋白，在骨再生治疗方面具有潜力。BMSCs 可能是一种治疗方法。在这项研究中，我们将 T2DM 大鼠的 BMSCs（BMSCs-D）和正常大鼠的 BMSCs（BMSCs-N）分开，鉴定它们分化为不同细胞类型的能力。然后，我们发现 BMSCs-D 中的 Sema3A 表达水平明显低于 BMSCs-N。Sema3A 刺激对 BMSCs 的增殖或迁移没有影响。然而，Sema3A 刺激显著增加了成骨相关基因的表达，包括 I 型胶原、碱性磷酸酶、Runt 相关转录因子 2（RUNX2）、骨形态发生蛋白和骨钙素。此外，Sema3A 刺激还增强了 BMSCs 的成骨能力。总之，我们证明了外源性 Sema3A 刺激可能修复 BMSCs-D 的成骨能力，从而为恢复 T2DM 患者受损的骨再生能力提供了一种新策略。
