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

Autor:	Julovi SM; Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia sohel.julovi@sydney.edu.au natasha.rogers@health.nsw.gov.au.; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Dao A; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Bioengineering & Molecular Medicine (BAMM) Laboratory, the Children's Hospital at Westmead and the Westmead Institute for Medical Research, Westmead, New South Wales, Australia., Trinh K; Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., O'Donohue AK; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Bioengineering & Molecular Medicine (BAMM) Laboratory, the Children's Hospital at Westmead and the Westmead Institute for Medical Research, Westmead, New South Wales, Australia., Shu C; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Raymond Purves Bone and Joint Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia., Smith S; Raymond Purves Bone and Joint Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia., Shingde M; Department of Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Wentworthville, New South Wales, Australia., Schindeler A; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Bioengineering & Molecular Medicine (BAMM) Laboratory, the Children's Hospital at Westmead and the Westmead Institute for Medical Research, Westmead, New South Wales, Australia., Rogers NM; Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia sohel.julovi@sydney.edu.au natasha.rogers@health.nsw.gov.au.; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia., Little CB; The Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.; Raymond Purves Bone and Joint Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	RMD open [RMD Open] 2023 Aug; Vol. 9 (3).
DOI:	10.1136/rmdopen-2023-003109
Abstrakt:	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<0.05), with accompanying reductions (p<0.05) in subchondral trabecular bone, bone volume and mineral density. DMM significantly (p<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<0.05) renal fibrosis, proteinuria and increased (p<0.05) 5/6Nx-induced serum urea. However, DMM in 5/6Nx-mice resulted in significantly reduced (p<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. Conclusion: This study assessed a world-first preclinical comorbid CKD-OA model. Our findings demonstrate significant bidirectional disease-modifying interaction between CKD and OA. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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