Role of the PERK-eIF2α-CHOP Signaling Pathway in the Effect of Needle Knife Therapy on Knee Joint Chondrocyte Apoptosis.

Yong-Hui Yang,Tian-Hao Liu,Li-Da Zhang,Zhu-Yue Chen,Xiao-Shuang Huang

doi:10.1155/2019/7164916

Abstract

Needle knife therapy, a form of acupuncture and moxibustion, has been widely used in the clinical treatment of knee osteoarthritis (KOA). However, the mechanism is not clear. Therefore, we studied the mechanisms of action of needle knife intervention on KOA in rabbits, with the PERK-eIF2α-CHOP pathway as a starting point, in order to determine the mechanism underlying knee joint chondrocyte apoptosis. Apoptosis and ultrastructural changes in the articular cartilage were examined by pathological study and transmission electron microscopy, and PERK, eIF2α, and CHOP mRNA and protein levels were detected by qRT-PCR and western blot, respectively. PERK, eIF2α, and CHOP protein levels were significantly higher in the model group than in the normal group (P < 0.01) and were considerably downregulated in the needle knife and the medicine groups compared to the model group (P < 0.01). The eIF2α, p-eIF2α, and CHOP protein levels were not significantly different between the needle knife and medicine groups. The PERK, eIF2α, and CHOP mRNA levels in the drug group were higher than those in the needle knife group (P < 0.01). Needle knife therapy can regulate PERK-eIF2α-CHOP signaling pathway, which could be one of the mechanisms by which it affects chondrocyte apoptosis in KOA rabbits.

Highlights

Knee osteoarthritis (KOA) is a chronic degenerative joint disease characterized by degeneration of joint cartilage
The knee joints of rabbits in the model group had relatively thin and clear cartilage layers with fewer chondrocytes; the surface layer of the cartilage was fibrotic, and the chondrocytes in each layer proliferated with slight osteofibrosis in some chondrocytes; the cartilage layer was significantly different from that of the normal group
We found that chondrocyte apoptosis was significantly higher in the KOA model group than in the normal group and was accompanied by pathological and morphological changes, indicating joint chondrocyte apoptosis in KOA

Summary

Introduction

Knee osteoarthritis (KOA) is a chronic degenerative joint disease characterized by degeneration of joint cartilage. KOA is associated with joint pain, swelling, deformity, and movement disorders. The pathogenesis of the disease has not been completely established, and no consensus has been reached on its clinical treatment, which often results in emotional and economic burdens to patients. Acupuncture and moxibustion have shown clear therapeutic effects on KOA and other diseases. A form of acupuncture and moxibustion, has shown favorable effects in the clinical treatment of KOA [1,2,3]. There have been several studies on the mechanisms underlying the effects of needle knife therapy, including the effects of needle knife intervention on the biomechanics of the patellar ligament [4, 5], matrix metalloproteinases, extracellular matrix, and inflammatory factors [6,7,8,9]

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