{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:11:22Z","timestamp":1788858682061,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy","award":["1032\/1\/13"],"award-info":[{"award-number":["1032\/1\/13"]}]},{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy","award":["882\/1\/12"],"award-info":[{"award-number":["882\/1\/12"]}]},{"award":["1032\/1\/13"],"award-info":[{"award-number":["1032\/1\/13"]}],"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"publisher"}]},{"award":["882\/1\/12"],"award-info":[{"award-number":["882\/1\/12"]}],"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Traditional open anterior cruciate ligament transection (ACLT) surgical models performed through arthrotomy may introduce capsular trauma and postoperative inflammatory responses that can interfere with the interpretation of post-traumatic osteoarthritis (OA). This study aimed to evaluate the feasibility of a minimally invasive, arthroscopic ACLT rabbit model performed entirely under arthroscopic visualization, without arthrotomy, using a 2.4-mm arthroscope and 2.5-mm shaver, and to provide preliminary structural, histological, synovial, and systemic biochemical characterization of the model for future therapeutic testing. Materials and Methods: Bilateral arthroscopic ACLT was performed in three skeletally mature New Zealand rabbits, followed by a supervised 12-week exercise protocol. Joint degeneration was evaluated macroscopically and histopathologically using the standardized Pritzker-Osteoarthritis Research Society International (OARSI) grading system. Collagen matrix remodeling was assessed via Picrosirius Red staining. Local intra-articular catabolism was quantified via Enzyme-Linked Immunosorbent Assay (ELISA) for matrix metallopeptidase 13 (MMP-13) and interleukin-1\u03b2 (IL-1\u03b2) from synovial fluid. Systemic oxidative stress, including lipid peroxidation biomarkers, malondialdehyde (MDA), and nitric oxide (NO), was evaluated in serum. Results: The arthroscopic approach induced osteoarthritic changes, with severity varying across the cohort. Histopathology revealed vertical matrix fissures and disruption of the normal columnar chondrocyte organization, yielding a median comprehensive Pritzker-OARSI score of 6 (range 6\u201310), with horizontal degradation restricted to stage 2. Synovial fluid analysis demonstrated measurable concentrations of MMP-13 (188.77 \u00b1 93.87 ng\/mL) and IL-1\u03b2 (174.93 \u00b1 95.51 pg\/mL). Furthermore, serum oxidative stress parameters at the 12-week endpoint included lipid peroxidation (MDA: 1.01 \u00b1 0.03 nmol\/mL) and NO levels (82.72 \u00b1 0.32 \u00b5mol\/L), presented descriptively in the absence of a comparator group. Conclusions: This study establishes the first multifaceted pathological baseline of a minimally invasive arthroscopic ACLT rabbit model before therapeutic intervention. The arthroscopic ACLT model produced structural cartilage degeneration alongside measurable intra-articular catabolic and systemic oxidative stress changes, establishing a baseline phenotype and a starting point for future therapeutic studies.<\/jats:p>","DOI":"10.3390\/medicina62091725","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:10:22Z","timestamp":1788855022000},"page":"1725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Arthroscopic Anterior Cruciate Ligament Transection for Osteoarthritis Induction in Rabbits: A Pilot Feasibility and Characterization Study"],"prefix":"10.3390","volume":"62","author":[{"given":"Alina Otilia","family":"Adam","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Traumatology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400132 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Horea Rares Ciprian","family":"Benea","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400132 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-1011","authenticated-orcid":false,"given":"Luciana-M\u0103d\u0103lina","family":"Gherman","sequence":"additional","affiliation":[{"name":"Experimental Centre, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-8963","authenticated-orcid":false,"given":"Daniel","family":"Oltean-Dan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400132 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Drago\u0219","family":"Apostu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400132 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-2882","authenticated-orcid":false,"given":"Dan","family":"Gheban","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0791","authenticated-orcid":false,"given":"Adrian","family":"Bogdan Tigu","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MEDFUTURE\u2014Institute for Biomedical Research, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6241-6901","authenticated-orcid":false,"given":"Andrei","family":"Ivancuta","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MEDFUTURE\u2014Institute for Biomedical Research, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7117-3598","authenticated-orcid":false,"given":"Alexandru Cristian","family":"Sabo","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MEDFUTURE\u2014Institute for Biomedical Research, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Andrada","family":"Uhl","sequence":"additional","affiliation":[{"name":"Department of Personalized Medicine and Rare Diseases, MEDFUTURE\u2014Institute for Biomedical Research, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Maria","family":"Cri\u0219an","sequence":"additional","affiliation":[{"name":"Department of Histology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tang, X., Peng, J.R., Deng, Y., Lan, S., Yen, Y., and Tang, Y. (2025). Global, Regional, and National Burden of Osteoarthritis among Middle-Aged and Older Adults: Estimates from the Global Burden of Disease Study 2021 and Projections to 2050. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1696929"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1590\/S0100-736X2013000300001","article-title":"Experimental Osteoarthritis in Rabbits: Lesion Progression","volume":"33","author":"Campos","year":"2013","journal-title":"Pesqui. Vet. Bras."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6","DOI":"10.23950\/jcmk\/12629","article-title":"Osteoarthritis: A Contemporary View of the Problem, the Possibilities of Therapy and Prospects for Further Research","volume":"19","author":"Zaripova","year":"2022","journal-title":"J. Clin. Med. Kazakhstan"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1053\/joca.1998.0207","article-title":"The Effects of Hyaluronan on Matrix Metalloproteinase-3 (MMP-3), Interleukin-1\u00df (IL-1\u00df), and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Gene Expression during the Development of Osteoarthritis","volume":"7","author":"Takahashi","year":"1999","journal-title":"Osteoarthr. Cartil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"764621","DOI":"10.1155\/2012\/764621","article-title":"A Review of Translational Animal Models for Knee Osteoarthritis","volume":"2012","author":"Gregory","year":"2012","journal-title":"Arthritis"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Song, D.H., Kim, S.H., Jung, Y., and Kim, S.J. (2018). Development and Characterization of Various Osteoarthritis Models for Tissue Engineering. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194288"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00223-020-00670-x","article-title":"Models of Osteoarthritis: Relevance and New Insights","volume":"109","author":"Samvelyan","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"640","DOI":"10.2106\/JBJS.J.00150","article-title":"Instability Dependency of Osteoarthritis Development in a Rabbit Model of Graded Anterior Cruciate Ligament Transection","volume":"93","author":"Tochigi","year":"2011","journal-title":"J. Bone Jt. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/j.1600-0838.2005.00513.x","article-title":"A Capsular Incision Leads to a Fast Osteoarthritic Response, but Also Elevated Levels of Activated Osteogenic Protein-1 in Rabbit Knee Joint Cartilage","volume":"16","author":"Fahlgren","year":"2006","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1302\/0301-620X.43B4.752","article-title":"The etiology of chondromalacia patellae","volume":"43-B","author":"Outerbridge","year":"1961","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1007\/s11999.0000000000000255","article-title":"Classifications in Brief: Outerbridge Classification of Chondral Lesions","volume":"476","author":"Slattery","year":"2018","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.joca.2010.05.029","article-title":"The OARSI Histopathology Initiative\u2014Recommendations for Histological Assessments of Osteoarthritis in the Rabbit","volume":"18","author":"Laverty","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","article-title":"Osteoarthritis Cartilage Histopathology: Grading and Staging","volume":"14","author":"Pritzker","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9159","DOI":"10.1038\/s41598-022-13062-y","article-title":"Structural Changes in the Collagen Network of Joint Tissues in Late Stages of Murine OA","volume":"12","author":"Yoshioka","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1369\/00221554211046777","article-title":"Picrosirius Red Staining: Revisiting Its Application to the Qualitative and Quantitative Assessment of Collagen Type I and Type III in Tendon","volume":"69","author":"Coenen","year":"2021","journal-title":"J. Histochem. Cytochem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Adam-Bonci, T.I., Bonci, E.A., P\u00e2rvu, A.E., Herdean, A.I., Mo\u021b, A., Taulescu, M., Ungur, A., Pop, R.M., Boc\u0219an, C., and Irimie, A. (2021). Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137089"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Boarescu, I., Pop, R.M., Boarescu, P.M., Boc\u0219an, I.C., Gheban, D., Bulboac\u0103, A.E., Buzoianu, A.D., and Bolboac\u0103, S.D. (2023). Ginger (Zingiber officinale) Root Capsules Enhance Analgesic and Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation. Antioxidants, 12.","DOI":"10.3390\/antiox12030745"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"563","DOI":"10.4414\/smw.2003.10397","article-title":"Increased Oxidative Stress in Patients with Hydatidiform Mole","volume":"133","author":"Harma","year":"2003","journal-title":"Swiss Med. Wkly."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S1063-4584(05)80318-8","article-title":"Characterization of a Model of Osteoarthritis in the Rabbit Knee","volume":"4","author":"Yoshioka","year":"1996","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","first-page":"22","article-title":"Optimal Timing of Research after Anterior Cruciate Ligament Resection in Rabbits","volume":"43","author":"Papaioannou","year":"2004","journal-title":"Contemp. Top. Lab. Anim. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1002\/jor.25009","article-title":"Early Changes in Osteochondral Tissues in a Rabbit Model of Post-Traumatic Osteoarthritis","volume":"39","author":"Huang","year":"2021","journal-title":"J. Orthop. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1590\/S0102-865020160090000005","article-title":"Comparison between Two Different Experimental Models of Osteoarthritis in Rabbits. Intra-Articular Collagenase Injection and Anterior Cruciate Ligament Transection","volume":"31","author":"Hermeto","year":"2016","journal-title":"Acta Cir. Bras."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/jor.20720","article-title":"Assessment of the Efficacy of Joint Lavage in Rabbits with Osteoarthritis of the Knee","volume":"27","author":"Fu","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.joca.2015.08.001","article-title":"Establishment of a Rabbit Model to Study the Influence of Advanced Glycation End Products Accumulation on Osteoarthritis and the Protective Effect of Pioglitazone","volume":"24","author":"Li","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: Pathogenic Signaling Pathways and Therapeutic Targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1136\/ard.61.7.591","article-title":"Differential Expression Patterns of Matrix Metalloproteinases and Their Inhibitors during Development of Osteoarthritis in a Transgenic Mouse Model","volume":"61","author":"Salminen","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","first-page":"7094","article-title":"L-Monomethyl-Arginine Decreases Apoptosis of Chondrocytes by Altering Bax and Bcl-2 Expression in Osteoarthritis of Rabbit Knee","volume":"11","author":"Wang","year":"2012","journal-title":"Afr. J. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, C., He, Y., Li, Y., Wang, G., Liu, D., Cai, G., and He, C. (2021). A Novel Method to Establish the Rabbit Model of Knee Osteoarthritis: Intra-Articular Injection of SDF-1 Induces OA. BMC Musculoskelet. Disord., 22.","DOI":"10.1186\/s12891-021-04188-7"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40634-022-00501-y","article-title":"Developing an Experimental Model of Early Knee Osteoarthritis after Medial Meniscus Posterior Root Release: An in Vivo Study","volume":"9","author":"Dzidzishvili","year":"2022","journal-title":"J. Exp. Orthop."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"34423","DOI":"10.1038\/srep34423","article-title":"A Novel Rabbit Model of Early Osteoarthritis Exhibits Gradual Cartilage Degeneration after Medial Collateral Ligament Transection Outside the Joint Capsule","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12897","DOI":"10.7717\/peerj.12897","article-title":"Synovial Fluid Proteome Profile of Surgical versus Chemical Induced Osteoarthritis in Rabbits","volume":"10","author":"Tan","year":"2022","journal-title":"Peer J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tudorachi, N.B., Totu, E.E., Fifere, A., Ardeleanu, V., Mocanu, V., Mircea, C., Isildak, I., Smilkov, K., and C\u0103r\u0103u\u015fu, E.M. (2021). The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis. Antioxidants, 10.","DOI":"10.3390\/antiox10060985"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/art.37782","article-title":"Mitochondrial Dysfunction in Osteoarthritis Is Associated with Down-Regulation of Superoxide Dismutase 2","volume":"65","author":"Gavriilidis","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_34","first-page":"1855","article-title":"Oxidative Stress, Vitamin e, and Antioxidant Capacity in Knee Osteoarthritis","volume":"7","author":"Suantawee","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bertoni, L., Jacquet-Guibon, S., Branly, T., Legendre, F., Desanc\u00e9, M., Mespoulhes, C., Melin, M., Hartmann, D.J., Schmutz, A., and Denoix, J.M. (2020). An Experimentally Induced Osteoarthritis Model in Horses Performed on Both Metacarpophalangeal and Metatarsophalangeal Joints: Technical, Clinical, Imaging, Biochemical, Macroscopic and Microscopic Characterization. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235251"},{"key":"ref_36","first-page":"6979585","article-title":"Evaluation of Chondroprotective Activity of Channa Striatus in Rabbit Osteoarthritis Model","volume":"2019","author":"Omar","year":"2019","journal-title":"BioMed Res. Int."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1725\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:48:42Z","timestamp":1788857322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["medicina62091725"],"URL":"https:\/\/doi.org\/10.3390\/medicina62091725","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}