MISS NANDITA RAM1, DR SOHEL JULOVI1,2, DR AIKEN DAO3, DR KATIE TRINH1, MISS ALEXANDRA O’DONOHUE3, MRS SUSAN SMITH4, DR CINDY SHU4, DR JENNIFER LI1, DR MEENA SHINGDE2, ASSOCIATE PROFESSOR AARON SCHINDELER2,3, PROFESSOR CHRISTOPHER LITTLE2,4, ASSOCIATE PROFESSOR NATASHA ROGERS1,2
1Kidney Injury Group, The Westmead Institute For Medical Research, Westmead, Australia, 2The Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia, 3Bioengineering & Molecular Medicine (BAMM) Laboratory, The Children’s Hospital at Westmead, Westmead, Australia, 4Raymond Purves Bone and Joint Laboratory, Kolling Institute, St. Leonards, Australia
Background: The prevalence of co-morbid conditions of chronic kidney disease (CKD) and osteoarthritis (OA) are increasing on a global scale. The reasons are not known.
Aims: The aims of the study were to develop a preclinical co-morbid model for CKD and OA and to investigate the influence of CKD on OA progression.
Methods: Male C57BL/6 (B6) mice were subjected to 5/6 nephrectomy (5/6Nx) and/or destabilisation of medial meniscus (DMM) surgery. Mice were assigned to Sham, 5/6Nx, DMM, and 5/6Nx+DMM groups. Ten weeks after DMM, OA phenotype were assessed, and bone changes were measured by micro computed tomography (μCT). Osteoclastic and matrix metalloproteinase (MMP)-13 activity and bone metabolic markers were analysed. Phenotyping of CKD was also performed.
Results: 5/6Nx model recapitulates characteristic features of CKD in B6 mice. 5/6Nx increased osteoclastic activity in the subchondral bone, and decreased subchondral trabeculae (BV/TV, pTb.N, and pTb.Th) and volumetric bone mineral density (vBMD) compared to sham and DMM. Consistently, serum alkaline phosphatase, Ca+2 and PO4-3 were increased in 5/6Nx mice. Histological assessment indicated that cartilage damage, subchondral bone pathology, synovitis, meniscus injury, osteophytes formation and enthesophytes were increased in DMM mice. Unexpectedly, 5/6Nx reduces DMM-induced cartilage damage while demonstrating significantly increased injury, MMP13 expression and osteoclastic activity in the meniscus.
Conclusion: This study assessed a world-first preclinical CKD-OA model, demonstrating that changes in subchondral bone microstructure and remodeling is independent of cartilage injury in CKD mice.
Biography:
Nandita Ram completed her Bachelor of Science degree at The University of Sydney, majoring in Applied Medical Science and Pharmacology. She is currently completing her honours year with the Kidney Injury Group, Centre for Transplant and Renal Research at The Westmead Institute for Medical Research. Her research project involves investigating osteoarthritis in chronic kidney disease.