Plenary Poster 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

Chondrocyte glucocorticoid receptor deletion attenuates cartilage damage in murine osteoarthritis (#25)

Eugenie Macfarlane 1 , Jan Tuckermann 2 , Markus J Seibel 1 , Hong Zhou 1
  1. Bone Research Program, ANZAC Research Institute, The University of Sydney, Concord, NSW, Australia
  2. Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany

Although glucocorticoids (GCs) are often used in the treatment of osteoarthritis (OA) for pain relief, the role of endogenous GCs in the pathogenesis of OA remains unknown. We have previously shown that disruption of endogenous GC signaling in osteoblasts and osteocytes mitigates OA in mice by reducing the severity of cartilage damage, subchondral bone sclerosis and osteophyte formation. This finding led us to investigate whether disruption of endogenous GC signaling specifically in chondrocytes also affects the development of OA.

Osteoarthritis of the knee joint was induced by surgical destabilization of the medial meniscus (DMM) in tamoxifen-inducible glucocorticoid receptor-knockout (chGRKO) mice and their wild-type (WT) littermates at 22-weeks of age (n=10-11 per group). Sham surgery was used as a control (n=4-5 per group). Both WT-DMM and chGRKO-DMM mice developed apparent OA 16-weeks after surgery, characterized by cartilage degradation, subchondral bone sclerosis and osteophyte formation. No obvious signs of inflammation were observed histologically at this time point. Histological semiquantitative scoring revealed that compared to WT-DMM mice, cartilage damage was significantly less pronounced in chGRKO-DMM mice, particularly at the medial tibial plateau and femur condyle (Fig. 1A, B). Medial tibial cartilage area assessed by histomorphometry was 5912μm2 and 4632μm2 in chGRKO-DMM and WT-DMM mice respectively (p=0.0149; Fig. 1B). Similarly, intact medial femoral cartilage area was 6728μm2 and 5384μm2 in chGRKO-DMM and WT-DMM mice respectively (p=0.0116; Fig. 1B). Deletion of the glucocorticoid receptor in chondrocytes appeared to have no impact on subchondral bone sclerosis, osteophyte formation or synovial inflammation as no differences were observed between chGRKO-DMM and WT-DMM mice by either micro-CT or histomorphometry analyses (Fig. 1C).

We conclude that endogenous GC signaling in chondrocytes promotes cartilage degradation but not abnormal bone formation (subchondral bone sclerosis and osteophytes) in a mouse model of surgically induced OA.

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