{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T19:43:48Z","timestamp":1777319028068,"version":"3.51.4"},"reference-count":50,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Betty Schofield and Joyce Anderson Bequest Grant 2018, Westmead Medical Research Foundation"},{"name":"National Heart Foundation Vanguard Grant","award":["106035"],"award-info":[{"award-number":["106035"]}]},{"name":"National Health Medical Research Council","award":["GNT2007991"],"award-info":[{"award-number":["GNT2007991"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,7,28]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seventy (70) male 8\u201310\u2009week-old C57BL\/6 mice were subjected to 5\/6 nephrectomy (5\/6Nx)\u00b1destabilisation 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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&lt;0.05), with accompanying reductions (p&lt;0.05) in subchondral trabecular bone, bone volume and mineral density. DMM significantly (p&lt;0.05) increased tibiofemoral cartilage damage, subchondral bone sclerosis, marginal osteophytes and synovitis, in association with increased cartilage and synovial MMP-13. DMM alone induced (p&lt;0.05) renal fibrosis, proteinuria and increased (p&lt;0.05) 5\/6Nx-induced serum urea. However, DMM in 5\/6Nx-mice resulted in significantly reduced (p&lt;0.05) cartilage pathology and marginal osteophyte development, in association with reduced subchondral bone volume and density, and inhibition of 5\/6Nx-induced subchondral bone osteoclast activation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study assessed a world-first preclinical comorbid CKD-OA model. Our findings demonstrate significant bidirectional disease-modifying interaction between CKD and OA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003109","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T13:16:39Z","timestamp":1691673399000},"page":"e003109","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Disease-modifying interactions between chronic kidney disease and osteoarthritis: a new comorbid mouse model"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0834-2366","authenticated-orcid":false,"given":"Sohel M","family":"Julovi","sequence":"first","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia"},{"name":"The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 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