Chondroprotective Effects of Combination Therapy of Acupotomy and Human Adipose Mesenchymal Stem Cells in Knee Osteoarthritis Rabbits via the GSK3β-Cyclin D1-CDK4/CDK6 Signaling Pathway.
Chondroprotective Effects of Combination Therapy of Acupotomy and Human Adipose Mesenchymal Stem Cells in Knee Osteoarthritis Rabbits via the GSK3β-Cyclin D1-CDK4/CDK6 Signaling Pathway.
复制标题
通过 GSK3β-细胞周期蛋白 D1-CDK4/CDK6 信号通路针刀和人类脂肪间充质干细胞联合治疗膝骨关节炎兔的软骨保护作用
DOI：
10.14336/ad.2019.1104
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发表时间：
2020-10
影响因子：
7.4
通讯作者：
Guo C
中科院分区：
文献类型：
--
作者：
An X;Wang T;Zhang W;Yu H;Chunhua Zhao R;Guo Y;Wang C;Qin L;Guo C
脂肪来源的干细胞（ASCs）是高度软骨性的，可以通过减轻软骨缺陷来治疗膝骨关节炎（KOA）。针刀是一种以中医理论为指导的生物力学疗法，通过纠正异常力学来缓解软骨退化，在临床上广泛应用于KOA的治疗。然而，针刀联合ASCs是否能通过促进KOA家兔软骨细胞增殖来逆转软骨退变尚不清楚。本研究旨在探讨针刀联合ASCs对膝关节固定6周后KOA家兔软骨细胞增殖的影响，并探讨其作用机制。KOA造模后，五组家兔（针刀组、ASCs组、针刀+ ASCs组、模型组和对照组）接受指示干预4周。联合治疗显著恢复了koa诱导的膝关节被动活动范围（PROM）的减少，并降低了软骨退变标志物软骨寡聚基质蛋白（COMP）的血清升高水平。此外，磁共振成像（MRI）和扫描电镜（SEM）图像显示联合治疗对软骨损伤有抑制作用。联合治疗还显著阻断了软骨组织中糖原合成酶激酶3β (GSK3β) mRNA和蛋白表达的升高，以及细胞周期蛋白D1/CDK4和细胞周期蛋白D1/CDK6 mRNA和蛋白表达的降低。上述结果提示，联合治疗可减轻KOA家兔膝关节不动、促进软骨细胞增殖、减轻软骨退变，这些作用可能通过特异性调节GSK3β-cyclin D1-CDK4/CDK6通路介导。
Adipose-derived stem cells (ASCs) are highly chondrogenic and can be used to treat knee osteoarthritis (KOA) by alleviating cartilage defects. Acupotomy, a biomechanical therapy guided by traditional Chinese medicine theory, alleviates cartilage degradation and is widely used in the clinic to treat KOA by correcting abnormal mechanics. However, whether combining acupotomy with ASCs will reverse cartilage degeneration by promoting chondrocyte proliferation in KOA rabbits is unknown. The present study aimed to investigate the effects of combination therapy of acupotomy and ASCs on chondrocyte proliferation and to determine the underlying mechanism in rabbits with KOA induced by knee joint immobilization for 6 weeks. After KOA modeling, five groups of rabbits (acupotomy, ASCs, acupotomy + ASCs, model and control groups) received the indicated intervention for 4 weeks. The combination therapy significantly restored the KOA-induced decrease in passive range of motion (PROM) in the knee joint and reduced the elevated serum level of cartilage oligomeric matrix protein (COMP), a marker for cartilage degeneration. Furthermore, magnetic resonance imaging (MRI) and scanning electron microscopy (SEM) images showed that the combination therapy inhibited cartilage injury. The combination therapy also significantly blocked increases in the mRNA and protein expression of glycogen synthase kinase-3β (GSK3β) and decreases in the mRNA and protein expression of cyclin D1/CDK4 and cyclin D1/CDK6 in cartilage. These findings indicated that the combination therapy mitigated knee joint immobility, promoted chondrocyte proliferation and alleviated cartilage degeneration in KOA rabbits, and these effects may be mediated by specifically regulating the GSK3β-cyclin D1-CDK4/CDK6 pathway.