Disease-modifying interactions between chronic kidney disease and osteoarthritis: a new comorbid mouse model

Autor: Susan Smith, Christopher B Little, Aiken Dao, Sohel M Julovi, Katie Trinh, Alexandra K O’Donohue, Cindy Shu, Meena Shingde, Aaron Schindeler, Natasha M Rogers
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: RMD Open, Vol 9, Iss 3 (2023)
Druh dokumentu: article
ISSN: 2056-5933
DOI: 10.1136/rmdopen-2023-003109
Popis: Objective The prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism and consequences of concurrent CKD-OA are unclear. The aims of the study were to develop a preclinical comorbid model, and to investigate the disease-modifying interactions.Methods Seventy (70) male 8–10 week-old C57BL/6 mice were subjected to 5/6 nephrectomy (5/6Nx)±destabilisation of medial meniscus (DMM) or sham surgery. OA pathology and CKD were assessed 12 weeks postinduction by blinded histology scoring, micro-CT, immunohistochemistry for osteoclast and matrix metalloproteinase (MMP)-13 activity, and serum analysis of bone metabolic markers.Results The 5/6Nx model recapitulated characteristic features of CKD, with renal fibrosis and deranged serum alkaline phosphatase, calcium and phosphate. There was no histological evidence of cartilage pathology induced by 5/6Nx alone, however, synovial MMP-13 expression and subchondral bone osteoclastic activity were increased (p
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