Destabilization of the medial meniscus in geriatric mice captures functional decline in age-associated osteoarthritis
Abstract
Osteoarthritis (OA) disproportionately affects older adults, yet most preclinical models rely on young animals and fail to incorporate biological aging. Here, we establish a geriatric murine model of OA using destabilization of the medial meniscus (DMM) in 18-19-month-old C57BL/6J mice. Surgical induction produced joint pathology consistent with OA, including loss of cartilage integrity and osteophytic remodeling. Functionally, OA mice exhibited increased composite ethogram scores and reduced rearing behavior, indicating impaired mobility and weight-bearing capacity. These findings demonstrate that DMM surgery in aged mice induces both structural and functional features of OA. This model provides a practical and physiologically relevant platform for studying age-associated joint degeneration and evaluating therapeutics in an aging context.
References
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745-1759. doi:10.1016/S0140-6736(19)30417-9
Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20(10):739-744. doi:10.1097/01.bot.0000246468.80635.ef
Anderson DD, Chubinskaya S, Guilak F, et al. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. 2011;29(6):802-809. doi:10.1002/jor.21359
Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12(7):412-420. doi:10.1038/nrrheum.2016.65
Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res. 2016;11:19. Published 2016 Feb 2. doi:10.1186/s13018-016-0346-5
McCoy AM. Animal Models of Osteoarthritis: Comparisons and Key Considerations. Vet Pathol. 2015;52(5):803-818. doi:10.1177/0300985815588611
Glasson SS, Blanchet TJ, Morris EA. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis Cartilage. 2007;15(9):1061-1069. doi:10.1016/j.joca.2007.03.006
Loeser RF. The Role of Aging in the Development of Osteoarthritis. Trans Am Clin Climatol Assoc. 2017;128:44-54.
Jeon OH, Kim C, Laberge RM, et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med. 2017;23(6):775-781. doi:10.1038/nm.4324
Dunbar ML, David EM, Aline MR, Lofgren JL. Validation of a Behavioral Ethogram for Assessing Postoperative Pain in Guinea Pigs (Cavia porcellus). J Am Assoc Lab Anim Sci. 2016;55(1):29-34.
Inglis JJ, McNamee KE, Chia SL, et al. Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system. Arthritis Rheum. 2008;58(10):3110-3119. doi:10.1002/art.23870
Sturman O, Germain PL, Bohacek J. Exploratory rearing: a context- and stress-sensitive behavior recorded in the open-field test. Stress. 2018;21(5):443-452. doi:10.1080/10253890.2018.1438405
Glasson SS, Chambers MG, Van Den Berg WB, Little CB. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage. 2010;18 Suppl 3:S17-S23. doi:10.1016/j.joca.2010.05.025
Kalairaj MS, Pradhan R, Saleem W, Smith MM, Gaharwar AK. Intra-Articular Injectable Biomaterials for Cartilage Repair and Regeneration. Adv Healthc Mater. 2024;13(17):e2303794. doi:10.1002/adhm.202303794
Morici L, Allémann E, Rodríguez-Nogales C, Jordan O. Cartilage-targeted drug nanocarriers for osteoarthritis therapy. Int J Pharm. 2024;666:124843. doi:10.1016/j.ijpharm.2024.124843
Liao HJ, Chen HT, Chang CH. Peptides for Targeting Chondrogenic Induction and Cartilage Regeneration in Osteoarthritis. Cartilage. Published online September 18, 2024. doi:10.1177/19476035241276406
Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018;19(7):1987. Published 2018 Jul 7. doi:10.3390/ijms19071987
Ewart D, Harper L, Gravely A, Miller RA, Carlson CS, Loeser RF. Naturally occurring osteoarthritis in male mice with an extended lifespan. Connect Tissue Res. 2020;61(1):95-103. doi:10.1080/03008207.2019.1635590