Objective: Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degradation driven by matrix-degrading enzymes. Reproducible ex vivo models are essential for studying early degenerative processes and evaluating potential therapeutics. However, there remains a lack of accessible, cost-effective models that accurately replicate the biochemical environment and early-stage damage of OA. This study aimed to develop and validate a bovine cartilage explant model that replicates key features of early OA through enzymatic induction of tissue damage.
Methods: Bovine stifle cartilage explants were exposed to combinations of matrix metalloproteinases, aggrecanases, and cartilage biomarkers. Tissue damage was evaluated histologically, and semiquantitative scoring was used to assess structural changes. Statistical analyses were conducted to determine differences between treatment groups.
Results: Enzyme-treated samples exhibited significantly greater cartilage degradation compared to controls. The addition of cartilage oligomeric matrix protein (COMP) increased tissue damage, suggesting an active role in matrix destabilization. In contrast, the inclusion of TIMP-3, a known protease inhibitor, did not reduce degradation, raising questions about its protective efficacy in this context.
Conclusion: This chemically induced bovine model successfully simulates early cartilage degeneration consistent with OA pathology. Supported by recent literature on the roles of MMPs, ADAMTS-5, and COMP in joint disease, the model offers a valuable platform for future studies on OA mechanisms and therapeutic screening.
| [1] |
S. L. James, D. Abate, K. H. Abate, et al., “Global, Regional, and National Incidence, Prevalence, and Years Lived With Disability for 354 Diseases and Injuries for 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017,” Lancet 392, no. 10159 (2018): 1789–1858, https://doi.org/10.1016/s0140-6736(18)32279-7.
|
| [2] |
D. Pereira, E. Ramos, and J. Branco, “Osteoarthritis,” Acta Médica Portuguesa 28, no. 1 (2015): 99–106, https://doi.org/10.20344/amp.5477.
|
| [3] |
K. Zhou, Y.-J. Li, E. J. Soderblom, et al., “A Best-In-Class Systemic Biomarker Predictor of Clinically Relevant Knee Osteoarthritis Structural and Pain Progression,” Science Advances 9, no. 4 (2023): 1–14.
|
| [4] |
B. Grillet, R. V. S. Pereira, J. Van Damme, et al., “Matrix Metalloproteinases in Arthritis: Towards Precision Medicine,” Nature Reviews Rheumatology 19 (2023): 363–377, https://doi.org/10.1038/s41584-023-00966-w.
|
| [5] |
S. Tseng, A. H. Reddi, and P. E. Di Cesare, “Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis,” Biomarker Insights 4 (2009): 33–44, https://doi.org/10.4137/bmi.s645.
|
| [6] |
G. Zeng, A. Chen, W. Li, J. Song, and C. Gao, “High MMP-1, MMP-2, and MMP-9 Protein Levels in Osteoarthritis,” Genetics and Molecular Research 14 (2015): 14811–14822.
|
| [7] |
Y.-O. Son, “Estrogen-Related Receptor γ Causes Osteoarthritis by Upregulating Extracellular Matrix-Degrading Enzymes,” Nature Communications 8 (2017): 1–11.
|
| [8] |
M. A. Pratta, W. Yao, C. Decicco, et al., “Aggrecan Protects Cartilage Collagen From Proteolytic Cleavage,” Journal of Biological Chemistry 278, no. 46 (2003): 45539–45545, https://doi.org/10.1074/jbc.M303737200.
|
| [9] |
L. Jiang, J. Lin, S. Zhao, et al., “ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies,” Frontiers in Molecular Biosciences 8, no. 9 (2021): 703110, https://doi.org/10.3389/fmolb.2021.703110.
|
| [10] |
S. M. Ling, D. D. Patel, P. Garnero, et al., “Serum Protein Signatures Detect Early Radiographic Osteoarthritis,” Osteoarthritis and Cartilage 17, no. 1 (2009): 43–48, https://doi.org/10.1016/j.joca.2008.05.004.
|
| [11] |
M. Takizawa, E. Ohuchi, H. Yamanaka, et al., “Production of Tissue Inhibitor of Metalloproteinases 3 Is Selectively Enhanced by Calcium Pentosan Polysulfate in Human Rheumatoid Synovial Fibroblasts,” Arthritis and Rheumatism 43, no. 4 (2000): 812–820, https://doi.org/10.1002/1529-0131(200004)43:4<812::AID-ANR11>3.0.CO;2-Y.
|
| [12] |
A. Amour, P. M. Slocombe, A. Webster, et al., “TNF-Alpha Converting Enzyme (TACE) is Inhibited by TIMP-3,” FEBS Letters 435 (1998): 39–44.
|
| [13] |
C. Papaneophytou, A. Alabajos-Cea, E. Viosca-Herrero, et al., “Associations Between Serum Biomarkers of Cartilage Metabolism and Serum Hyaluronic Acid, With Risk Factors, Pain Categories, and Disease Severity in Knee Osteoarthritis: A Pilot Study,” BMC Musculoskeletal Disorders 23, no. 1 (2022): 195, https://doi.org/10.1186/s12891-022-05133-y.
|
| [14] |
A. Kondhalkar, R. Ambad, N. Bhatt, and R. K. Jha, “Determination of Clinical Utility of Novel Biochemical Markers in Osteoarthritis,” Journal of Pharmaceutical Research International 240-245 (2021): 240–245, https://doi.org/10.9734/jpri/2021/v33i39A32166.
|
| [15] |
K. Riewruja, S. Phakham, P. Sompolpong, et al., “Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis,” International Journal of Molecular Sciences 23, no. 2 (2022): 890, https://doi.org/10.3390/ijms23020890.
|
| [16] |
B. C. Sondergaard, K. Henriksen, H. Wulf, et al., “Relative Contribution of Matrix Metalloprotease and Cysteine Protease Activities to Cytokine-Stimulated Articular Cartilage Degradation,” Osteoarthritis and Cartilage 14, no. 8 (2006): 738–748, https://doi.org/10.1016/j.joca.2006.01.016.
|
| [17] |
E. U. Sumer, B. C. Sondergaard, J. C. Rousseau, et al., “MMP and Non-MMP-Mediated Release of Aggrecan and Its Fragments From Articular Cartilage: A Comparative Study of Three Different Aggrecan and Glycosaminoglycan Assays,” Osteoarthritis and Cartilage 15, no. 2 (2007): 212–221, https://doi.org/10.1016/j.joca.2006.07.009.
|
| [18] |
S. H. Madsen, E. U. Sumer, A. C. Bay-Jensen, B. C. Sondergaard, P. Qvist, and M. A. Karsdal, “Aggrecanase- and Matrix Metalloproteinase-Mediated Aggrecan Degradation Is Associated With Different Molecular Characteristics of Aggrecan and Separated in Time Ex Vivo,” Biomarkers 15, no. 3 (2010): 266–276, https://doi.org/10.3109/13547500903521810.
|
| [19] |
K. C. Ravindra, C. C. Ahrens, Y. Wang, et al., “Chemoproteomics of Matrix Metalloproteases in a Model of Cartilage Degeneration Suggests Functional Biomarkers Associated With Posttraumatic Osteoarthritis,” Journal of Biological Chemistry 293, no. 29 (2018): 11459–11469, https://doi.org/10.1074/jbc.M117.818542.
|
RIGHTS & PERMISSIONS
2025 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.
PDF
