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

Hasmik J. Samvelyan, Carmen Huesa, Lucy Cui Lin, Colin Farquharson, Katherine Staines

Research output: Contribution to journalArticlepeer-review

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. Cite this article: Bone Joint Res 2022;11(3):162-170.

Original languageEnglish
Pages (from-to)162-170
Number of pages9
JournalBone & Joint Research
Volume11
Issue number3
Early online date11 Mar 2022
DOIs
Publication statusPublished - Mar 2022

Keywords

  • Role Of Accelerated Growth Plate Fusion
  • The Absence
  • SOCS2
  • Osteoarthritis
  • Vulnerability

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