CCL22 is a biomarker of cartilage injury and plays a functional role in chondrocyte apoptosis

Cytokine. 2019 Mar:115:32-44. doi: 10.1016/j.cyto.2018.11.030. Epub 2019 Jan 7.

Abstract

Background: Osteoarthritis (OA) is one of the leading causes of disability worldwide. Previous history of knee injury is a significant risk factor for OA. It has been established that low-level chronic inflammation plays a pivotal role in the onset and pathogenesis of OA. The primary aim of this research was to determine if a history of knee joint injury is associated with systemic inflammation. A secondary aim was to determine if systemic inflammation is related to knee pain and joint structure.

Methods: Differences in serum cytokine association networks, knee joint structural changes (MRI), and self-reported pain (i.e., Knee Injury and Osteoarthritis Outcome Score Pain subscale, KOOSPAIN and Intermittent and Constant Osteoarthritis Pain score, ICOAP) between individuals who had sustained a youth (aged 15-26 years) sport-related knee injury 3-10 years previously and age- and sex-matched controls were examined. Proteins of interest were also examined in an OA rat model.

Results: Cytokine association networks were found to differ significantly between study groups, yet no significant associations were found between networks and KOOSPAIN or MRI-defined OA. A group of cytokines (MCP1/CCL2, CCL22 and TNFα) were differentially associated with other cytokines between study groups. In a pre-clinical rat OA model, serum CCL22 levels were associated with pain (r = 0.255, p = 0.045) and structural changes to the cartilage. CCL22 expression was also observed in human OA cartilage and furthermore, CCL22 induced apoptosis of isolated human chondrocytes.

Discussion: These results suggest that CCL22 may be an early factor in the onset/pathogenic process of cartilage degeneration and/or related to pain OA.

Keywords: Apoptosis; CCL22; Cartilage; Chemokine; Inflammation; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Apoptosis / physiology*
  • Biomarkers / metabolism*
  • Cartilage, Articular / metabolism*
  • Chemokine CCL22 / metabolism*
  • Chondrocytes / metabolism*
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation / metabolism
  • Knee / pathology
  • Knee Injuries / metabolism*
  • Knee Joint / metabolism
  • Male
  • Osteoarthritis, Knee / metabolism
  • Pain / metabolism
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Biomarkers
  • CCL22 protein, human
  • Chemokine CCL22
  • Cytokines
  • Tumor Necrosis Factor-alpha

Grants and funding