Advancing Osteoarthritis Research: Insights from Rodent Models and Emerging Trends

Abstract

Osteoarthritis (OA) is a degenerative joint disease that affects millions of individuals worldwide, causing pain, disability, and a significant burden on public health. Preclinical research using animal models is essential to our understanding of the underlying pathogenesis of OA and developing therapeutic strategies. Rodent models, in particular, have become indispensable in studying OA due to their ability to mimic various features of human disease. This review provides an overview of commonly used rodent models of OA, including surgical induction (e.g., destabilization of the medial meniscus and anterior cruciate ligament transection), chemical induction (e.g., monoiodoacetate-induced cartilage degeneration), and genetically modified models. Additionally, age-related OA models that naturally develop OA-like symptoms in aged rodents are also discussed. Despite their utility, rodent models face limitations in fully recapitulating the complexity of human OA. Emerging trends in OA research, including the use of 3D imaging for joint analysis, molecular profiling for deeper insights into disease mechanisms, and advancements in biomarkers for early detection and treatment, are highlighted. These innovations provide new opportunities to refine existing models and enhance the translation of findings to clinical therapies. This critical review provides comprehensive information for researchers working in OA and related fields, promoting a better understanding of the available rodent models and their applications in OA research.

Keywords: Inflammation; Joint inflammation; Osteoarthritis; Preclinical research; Reactive oxygen species; Rodent models.

Figure 1:

Pathophysiology and Molecular Mechanisms of Osteoarthritis. ADMTS4/5, ADAM metallopeptidase with thrombospondin type 1 motif 4/5; AMPK, adenosine monophosphate (AMP)-activated protein kinase; APC, adenomatous polyposis coli; DAMP, damage associated molecular patterns; Hes1, hairy and enhancer of split-1; ICAM1, intercellular adhesion molecule-1; IL1β, interleukin 1 beta; IL-6, interleukin 6; MMPs, matrix metallopeptidase; mTORC1, mammalian target of rapamycin complex 1; LDL, low-density lipoprotein; MMPs, matrix metallopeptidase; MYD88, myeloid differentiation primary response 88; NADPH, nicotinamide adenine dinucleotide phosphate NEMO, NF-kappa-B essential modulator; NF-κB, nuclear factor-kappa beta; PAMP, pathogen-associated molecular pattern molecules; RAGE, Receptor for Advanced Glycation Endproducts; ROS, reactive oxygen species; SMAD2/3/4, mothers against decapentaplegic homolog; TAK1, transforming growth factor-β-activated kinase 1; TGFβ, transforming growth factor-β; TLRs, toll like receptors; TNFα, tumor necrosis factor alpha; TRAF6, tumor necrosis factor receptor associated factor 6; VCAM1, vascular cell adhesion molecule 1; WNT, wingless-type MMTV integration site.

Figure 2:

Type of rodent model used to induce osteoarthritis (OA). Del1, developmental endothelial locus-1; Prg4, proteoglycan 4; RunX2/3, runt-related transcription factors; TIMP-3, tissue inhibitor of metalloproteinases-3.