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

Oncotarget. 2017 Jun 13;8(24):38602-38617. 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.

Keywords: TLR-2/NF-κB signaling pathway; Toll-like receptor 2; degenerative osteoarthritis; matrix metalloprotease-13; nuclear transcription factor-kappa B.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • China / epidemiology
  • Chondrocytes
  • Female
  • Follow-Up Studies
  • Humans
  • In Vitro Techniques
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism*
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Osteoarthritis, Knee / epidemiology*
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology*
  • Prevalence
  • Prognosis
  • Signal Transduction
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Biomarkers, Tumor
  • NF-kappa B
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • MMP13 protein, human
  • Matrix Metalloproteinase 13