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bioRxiv · 10.1101/2021.05.13.444074

The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability

Samvelyan, H. J.·Huesa, C.·Cui Lin, L.·Farquharson, C.·Staines, K. A.
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Abstract

Osteoarthritis is the most prevalent systemic musculoskeletal disorder characterised by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here we sought to examine the contribution of accelerated growth to osteoarthritis development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2-/-) display accelerated bone growth. We examined vulnerability of Socs2-/- mice to osteoarthritis following surgical induction of disease (destabilisation of the medial meniscus (DMM)), and with ageing, by histology and micro-CT. We observed significant increase in number (WT DMM: 532{+/-}56; WT sham: 495{+/-}45; KO DMM: 169{+/-}49; KO sham: 187{+/-}56; P<0.01) and density (WT DMM: 2.2{+/-}0.9; WT sham: 1.2{+/-}0.5; KO DMM: 13.0{+/-}0.5; KO sham: 14.4{+/-}0.7) of growth plate bridges in Socs2-/- in comparison to wild-type (WT). Histological examination of WT and Socs2-/- knees revealed articular cartilage damage with DMM in comparison to sham (WT DMM: 3.4{+/-}0.4; WT sham: 0.3{+/-}0.05 (P<0.05); KO DMM: 3.2{+/-}0.8; KO sham: 0.8{+/-}0.3). Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2-/- mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number and thickness in the medial compartment of Socs2-/-, in comparison to WT (P<0.001). DMM had no effect on the SCB thickness in comparison to sham in either genotype. Together these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on osteoarthritis vulnerability in this model. Summary statementDeletion of SOCS2 results in accelerated growth plate fusion, however this has no effect on osteoarthritis vulnerability.

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Samvelyan, H. J., Huesa, C., Cui Lin, L., Farquharson, C., Staines, K. A.. 2021-05-15. The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability. https://doi.org/10.1101/2021.05.13.444074

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