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

Samvelyan, Hasmik Jasmine; Huesa, Carmen; Cui, Lin; Farquharson, Colin; Staines, Katherine Ann

Abstract

Aims
Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA 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.

Methods
We examined vulnerability of Socs2-/- mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT.

Results
We observed a significant increase in mean number (wild-type (WT) DMM: 532 (SD 56); WT sham: 495 (SD 45); knockout (KO) DMM: 169 (SD 49); KO sham: 187 (SD 56); p < 0.001) and density (WT DMM: 2.2 (SD 0.9); WT sham: 1.2 (SD 0.5); KO DMM: 13.0 (SD 0.5); KO sham: 14.4 (SD 0.7)) of growth plate bridges in Socs2-/- in comparison with WT. Histological examination of WT and Socs2-/- knees revealed articular cartilage damage with DMM in comparison to sham. 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 with WT (p < 0.001). DMM had no effect on the SCB thickness in comparison with sham in either genotype.

Conclusion
Together, these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on OA vulnerability in this model.

Citation

Samvelyan, H. J., Huesa, C., Cui, L., Farquharson, C., & Staines, K. A. (2022). The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability. Bone & Joint Research, 11(3), 162-170. https://doi.org/10.1302/2046-3758.113.bjr-2021-0259.r1

• Journal Article Type: Article
• Online Publication Date: Mar 11, 2022
• Publication Date: 2022-03
• Deposit Date: Mar 14, 2022
• Journal: Bone & Joint Research
• Print ISSN: 2046-3758
• Publisher: British Editorial Society of Bone and Joint Surgery
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 3
• Pages: 162-170
• DOI: https://doi.org/10.1302/2046-3758.113.bjr-2021-0259.r1
• Public URL: http://researchrepository.napier.ac.uk/Output/2853237