Department of Spine Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Zhongshan Road 321, Nanjing, 210008, China.
Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
J Orthop Surg Res. 2022 Feb 9;17(1):82. doi: 10.1186/s13018-022-02978-w.
Abnormal metabolic features have been previously described in adolescent idiopathic scoliosis (AIS) patients. As an important regulator involved in energy metabolism, DPP-4 activity was reported to be remarkably decreased in osteoblasts of AIS patients. To date, there was still a lack of knowledge concerning the role of DPP-4 in the myogenesis of AIS.
Circulation DPP-4 level was assessed in the serum of 80 AIS girls and 50 healthy controls by ELISA. Myoblasts were purified from muscle specimens of AIS patients and LDH controls, and then treated with metabolic effectors including glucose and insulin. CCK-8 assay was used to assess the cell viability and myotube fusion index was calculated to evaluate myogenesis ability. Gene expressions of downstream signals of DPP-4 were evaluated by RT-qPCR and Western blot respectively.
AIS girls had remarkably down-expressed DPP-4 in both serum level (0.76 fold) and tissue (0.68 fold) level. Treatment with metabolic effectors led to significantly increased DPP-4 expression in the control cells, while there was no increase of DPP-4 in AIS cells. CCK-8 assay showed that the proliferation rate of control cells was significantly increased after being treated. Remarkably higher fusion index was also observed in the treated control cells. By contrast, the fusion index and cell proliferation rate were comparable between the treated and the untreated AIS cells.
Our study suggested a potential role of DPP-4 in abnormal metabolic condition of AIS patients. Compared with control cells, AIS myoblasts presented obviously impaired sensitivity to the treatment of glucose and insulin. Aberrant DPP-4 expression could lead to impaired insulin sensitivity in myoblasts and further influence the cell viability during myogenesis. The molecular mechanism connecting DPP-4 and insulin-related signaling in AIS is worthy of further investigation.
先前的研究表明，青少年特发性脊柱侧凸（AIS）患者存在异常代谢特征。DPP-4 作为一种参与能量代谢的重要调节剂，其在 AIS 患者成骨细胞中的活性显著降低。迄今为止，DPP-4 在 AIS 肌生成中的作用仍知之甚少。
通过 ELISA 检测 80 例 AIS 女孩和 50 名健康对照者血清中的 DPP-4 水平。从 AIS 患者和 LDH 对照者的肌肉标本中纯化肌母细胞，然后用代谢效应物（包括葡萄糖和胰岛素）处理。CCK-8 法检测细胞活力，计算肌管融合指数评估肌生成能力。分别通过 RT-qPCR 和 Western blot 检测 DPP-4 下游信号的基因表达。
AIS 女孩的血清（0.76 倍）和组织（0.68 倍）中 DPP-4 的表达均显著下调。代谢效应物处理后，对照组细胞中 DPP-4 的表达明显增加，而 AIS 细胞中 DPP-4 的表达没有增加。CCK-8 法检测结果显示，对照组细胞经处理后增殖率显著增加。处理后的对照组细胞也观察到显著较高的融合指数。相比之下，处理组和未处理组 AIS 细胞之间的融合指数和细胞增殖率相当。
我们的研究提示 DPP-4 可能在 AIS 患者异常代谢状态中发挥作用。与对照细胞相比，AIS 肌母细胞对葡萄糖和胰岛素的治疗反应明显受损。异常的 DPP-4 表达可能导致肌母细胞胰岛素敏感性受损，并进一步影响肌生成过程中的细胞活力。DPP-4 与 AIS 中胰岛素相关信号的分子机制值得进一步研究。
