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

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.

The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics

“…Knee joints were analysed at 4 and 14 weeks post-trauma for joint mineralisation and histology and at 6 weeks post-trauma for ACL mechanics and compared to aged-matched healthy knee joints. At 6 weeks post-trauma, PTOA progression in this model has been previously described and includes significant loss of hyaline articular cartilage in the lateral femur [ 24 ]. This indicates early stages of PTOA development at 6 weeks post-trauma.…”

Fibroblast Growth Factors and Cellular Communication Network Factors: Intimate Interplay by the Founding Members in Cartilage

“…In articular cartilage, the co-presence of CCN2 and FGF-2 was indicated in the pericellular matrix of chondrocytes [ 72 ], and the roles of these two proteins in osteoarthritis development is highly controversial. In one study, postnatal and cartilage-specific deletion of floxed CCN2 by tamoxifen-inducible Cre under the control of an Acan promoter conferred no significant effect on OA development [ 79 ], and global CCN2 deletion after birth by human ubiquitin C promoter-driven Cre even added resistance against OA in the other [ 72 ]. The difference between the two suggests some role of CCN2 acting in paracrine and/or endocrine fashions in OA development.…”

CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis

“…CTGF are widely distributed in other joint tissues such as synovium and bone ( 63 ). Selective deletion of CTGF might have different effects from global deletion ( 56 ). Different types of OA models represent different pathologies which might affect the microenvironment of CTGF.…”