Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis: an in vivo and in vitro study.

Yi-Xun Liu,Yong-Le Zhang,Xiao Wang,Tian-Lun Zhang,Guo-Dong Wang

doi:10.18632/oncotarget.16199

Abstract

The study aims to explore the effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis (OA). Degenerative knee OA and normal cartilage samples were collected from patients with degenerative knee OA receiving total knee arthroplasty and amputation. Expressions of TLR-2, NF-κB and MMP-13 were determined by qRT-PCR and immunochemistry. The chondrocytes were divided into control, IL-1β, IL-1β + anti-TLR-2 and IL-1β + PDTC groups. MTT assay and flow cytometry were performed to determine proliferation and apoptosis of the chondrocytes. Expressions of TLR-2, NF-κB and MMP-13 were measured by Western blotting. ELISA was conducted to detect the expressions of related inflammatory factors. The positive expressions of TLR, NF-κB and MMP13 were associated with body mass index (BMI), family history, exercise, and WOMAC scores of OA patients. Logistic regression analysis showed that OA influencing factors were TLR, NF-κB, MMP13, BMI, family history and exercise. Compared with normal chondrocytes, the expressions of TLR-2, NF-κB, MMP-13 and related inflammatory factors increased in degenerative knee OA. The chondrocytes in the IL-1β + anti-TLR-2 and IL-1β + PDTC groups showed lower apoptosis rates than those in the IL-1β group. Compared with the control group, increased expressions of TLR-2, NF-κB, phosphorylated-NF-κB (p-NF-κB), MMP-13, IL-1, IL-6 and TNF-α were found in the IL-1β group. In the IL-1β + anti-TLR-2 and IL-1β + PDTC groups, decreased expressions of NF-κB, p-NF-κB, MMP-13, IL-1, IL-6 and TNF-α were found compared with those in the IL-1β group. TLR-2/NF-κB signaling pathway contributes to the occurrence of degenerative knee OA.

Highlights

Osteoarthritis (OA), a degenerative joint disease, is characterized by joint pain, stiffness and swelling, degeneration of articular cartilage, intra-articular inflammation with synovitis and changes in peri-articular and sub-chondral bone [1]
The positive expressions of Toll-like receptors (TLRs), NF-kB, MMP13 were associated with body mass index (BMI), family history, exercise, and WOMAC scores of OA patients, but age, gender, smoking, drinking and tea drinking habits showed no significant difference
Signaling pathway in OA and the expressions of related inflammatory factors, with the main conclusion that expressions of TLR-2, NF-κB and matrix metalloprotease-13 (MMP-13) and related inflammatory factors were up-regulated with the increase of degree of OA lesions, indicating that TLR-2/NF-κB signaling pathway can contribute to occurrence of OA

Summary

Introduction

Osteoarthritis (OA), a degenerative joint disease, is characterized by joint pain, stiffness and swelling, degeneration of articular cartilage, intra-articular inflammation with synovitis and changes in peri-articular and sub-chondral bone [1]. Subchondral bone sclerosis and progressive cartilage degaradation are thought as hallmarks of OA [5]. Degeneration of articular cartilage is proven to be the obvious feature of OA that eventually causes joint destruction, because of the imbalance of anabolic activities [6, 7]. Treatment for degenerative OA usually includes pharmacological and non-pharmacological modalities [8, 9]. Degenerative OA has poor prognosis, it is significant to explore the mechanisms for the pathogenesis and treatment of degenerative OA

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