Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2

Dis Model Mech. 2020 Jul 14;13(7):dmm044719. doi: 10.1242/dmm.044719.

Abstract

CCN2 is a matricellular protein involved in several crucial biological processes. In particular, CCN2 is involved in cartilage development and in osteoarthritis. Ccn2 null mice exhibit a range of skeletal dysmorphisms, highlighting its importance in regulating matrix formation during development; however, its role in adult cartilage remains unclear. The aim of this study was to determine the role of CCN2 in postnatal chondrocytes in models of post-traumatic osteoarthritis (PTOA). Ccn2 deletion was induced in articular chondrocytes of male transgenic mice at 8 weeks of age. PTOA was induced in knees either surgically or non-invasively by repetitive mechanical loading at 10 weeks of age. Knee joints were harvested, scanned with micro-computed tomography and processed for histology. Sections were stained with Toluidine Blue and scored using the Osteoarthritis Research Society International (OARSI) grading system. In the non-invasive model, cartilage lesions were present in the lateral femur, but no significant differences were observed between wild-type (WT) and Ccn2 knockout (KO) mice 6 weeks post-loading. In the surgical model, severe cartilage degeneration was observed in the medial compartments, but no significant differences were observed between WT and Ccn2 KO mice at 2, 4 and 8 weeks post-surgery. We conclude that Ccn2 deletion in chondrocytes does not modify the development of PTOA in mice, suggesting that chondrocyte expression of CCN2 in adults is not a crucial factor in protecting cartilage from the degeneration associated with PTOA.This article has an associated First Person interview with the first author of the paper.

Keywords: CCN2; Cartilage; Osteoarthritis; Post-traumatic; Transgenic mouse; Trauma-induced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cartilage, Articular / surgery
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Chondrogenesis
  • Connective Tissue Growth Factor / deficiency*
  • Connective Tissue Growth Factor / genetics
  • Disease Models, Animal
  • Gene Deletion
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoarthritis / etiology
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Stress, Mechanical
  • Time Factors

Substances

  • CCN2 protein, mouse
  • Connective Tissue Growth Factor