TGF-β1和BMP2在骨关节炎患者的关节软骨细胞中诱导的代谢特征  

Metabolic characteristics of TGF-β1 and BMP2 induced in articular chondrocytes of patients with osteoarthritis

作　　者：罗安玉[1] 刘瀚霖[1] 谢小飞 黄琛 LUO An-Yu;LIU Han-Lin;XIE Xiao-Fei;HUANG Chen(Department of Orthopaedics,Hanyang Hospital,Wuhan University of Science and Technology,Wuhan 430050,China)

机构地区：[1]武汉科技大学附属汉阳医院骨二科,武汉430050

出　　处：《中国免疫学杂志》2020年第15期1884-1888,共5页Chinese Journal of Immunology

摘　　要：目的:探究骨关节炎病理进程中,TGF-β或BMP信号对关节软骨细胞能量代谢的调控作用和机制。方法:从骨关节炎患者的关节软骨标本中分离原代关节软骨细胞进行体外培养,分别给予TGF-β1或BMP2体外处理48~72 h后,进行代谢评估,测定葡萄糖的摄取量、乳酸和ATP产量;同时进行线粒体压力测试评估线粒体氧化磷酸化水平。Western blot检测糖酵解代谢关键蛋白Glut1、HKⅠ、HKⅡ、LDHA的表达。结果:发现TGF-β1通过上调关键蛋白Glut1和HKⅡ的表达水平,刺激糖酵解代谢,抑制氧化磷酸化,维持软骨细胞的代谢稳态。相反,BMP2通过增强线粒体的氧化磷酸化代谢,诱导关节软骨细胞发生能量代谢的重编程,促进骨关节炎病情的发生发展。结论:研究结果证实TGF-β和BMP蛋白通过对骨关节炎患者的关节软骨细胞发挥不同的调控作用对骨关节炎的疾病进展产生不同影响,提示在骨关节炎病理背景下,TGF-β1和BMP2的异常表达会破坏关节软骨细胞代谢平衡,促进骨关节炎的病理进程。Objective:To explore the regulatory effect and mechanism of TGF-βor BMP signal on energy metabolism of articular chondrocytes in the pathological process of osteoarthritis.Methods:Primary articular chondrocytes were isolated from articular cartilage specimens of patients with osteoarthritis and cultured in vitro.After being treated with TGF-β1 or BMP2 for 48-72 h,metabolism was evaluated,glucose uptake,lactic acid and ATP production were measured,and mitochondrial oxidative phosphorylation was evaluated by mitochondrial stress test.Western blot was used to detect the expressions of Glut1,HKⅠ,HKⅡand LDHA,which are the key proteins of glycolysis.Results:TGF-β1 maintained the metabolic homeostasis of chondrocytes by up-regulating the expression of key proteins Glut1 and HKⅡ,stimulating glycolysis and inhibiting oxidative phosphorylation.On the contrary,BMP2 promoted the occurrence and development of osteoarthritis by enhancing the oxidative phosphorylation metabolism of mitochondria and inducing the reprogramming of energy metabolism in articular chondrocytes.Conclusion:The results confirm that TGF-βand BMP proteins have different regulatory effects on articular chondrocytes of patients with osteoarthritis and have different effects on the disease progression of osteoarthritis.It is suggested that under the pathological background of osteoarthritis,the abnormal expression of TGF-β1 and BMP2 will destroy the metabolic balance of articular chondrocytes and promote the pathological process of osteoarthritis.

关 键 词：骨关节炎 能量代谢 关节软骨细胞 TGF-Β1 BMP2 

分 类 号：R684.3[医药卫生—骨科学]