Objectives: To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice.
Methods: Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing.
Results: HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM.
Conclusions: T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.
目的: 观察2型糖尿病对小鼠下颌骨骨再生以及辅助性T细胞17（Th17）、调节性T细胞（Treg）相关因子表达的影响。方法: 将36只6周龄C57BL/6J雄性小鼠随机分为正常对照（NC）组和2型糖尿病（T2DM）组，小鼠下颌骨缺损建模当天（0 d）和术后7、14、28 d检测空腹血糖。于两组小鼠下颌骨缺损建模后7、14、28 d，通过苏木素-伊红（HE）染色观察下颌骨缺损愈合情况，通过免疫组织化学染色的方法观察下颌骨缺损内碱性磷酸酶（ALP）、Runt相关转录因子2（RUNX2）、叉头框蛋白P3（Foxp3）、维甲酸相关孤核受体γt（RORγt）和蛋白酪氨酸磷酸酶非受体型2（PTPN2）的表达情况。结果: HE染色结果显示：T2DM组小鼠的下颌骨缺损范围内新生骨的数量明显少于NC组。免疫组织化学染色结果显示：成骨相关蛋白ALP和RUNX2的表达在T2DM组的骨缺损内明显降低；另外，2型糖尿病小鼠下颌骨缺损范围内的RORγt阳性细胞数量增加，Foxp3阳性细胞数量减少，PTPN2的表达明显降低。结论: 2型糖尿病可以显著地抑制小鼠下颌骨骨再生过程，PTPN2的下降以及Treg-Th17向偏移可能为其潜在的分子机制。.
Keywords: T helper cell 17; bone regeneration; protein tyrosine phosphatase non-receptor type 2; regulatory T cell; type 2 diabetes mellitus.