{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:39:32Z","timestamp":1788817172026,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups (MSS, Republic of Korea)","doi-asserted-by":"publisher","award":["S3034590"],"award-info":[{"award-number":["S3034590"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNF\u03b1 levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.<\/jats:p>","DOI":"10.3390\/ijms25031714","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T11:35:34Z","timestamp":1706614534000},"page":"1714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-0192","authenticated-orcid":false,"given":"Seung Hee","family":"Choi","sequence":"first","affiliation":[{"name":"Joonghun Pharmaceutical Co., Ltd., 15 Gukhoe-daero 62-gil, Yeongdeungpo-gu, Seoul 07236, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Joonghun Pharmaceutical Co., Ltd., 15 Gukhoe-daero 62-gil, Yeongdeungpo-gu, Seoul 07236, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul Gi","family":"Jang","sequence":"additional","affiliation":[{"name":"Joonghun Pharmaceutical Co., Ltd., 15 Gukhoe-daero 62-gil, Yeongdeungpo-gu, Seoul 07236, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Joonghun Pharmaceutical Co., Ltd., 15 Gukhoe-daero 62-gil, Yeongdeungpo-gu, Seoul 07236, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Young","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi Ryang","family":"Kweon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jeong","family":"Ryu","sequence":"additional","affiliation":[{"name":"Joonghun Pharmaceutical Co., Ltd., 15 Gukhoe-daero 62-gil, Yeongdeungpo-gu, Seoul 07236, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/ar74","article-title":"What can we do about osteoarthritis?","volume":"2","author":"Lohmander","year":"2000","journal-title":"Arthritis Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ozeki, N., Koga, H., and Sekiya, I. (2022). Degenerative Meniscus in Knee Osteoarthritis: From Pathology to Treatment. Life, 12.","DOI":"10.3390\/life12040603"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1302\/2046-3758.1112.BJR-2022-0215.R1","article-title":"Molecular crosstalk between articular cartilage, meniscus, synovium, and subchondral bone in osteoarthritis","volume":"11","author":"WWang","year":"2022","journal-title":"Bone Joint Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13075-023-03006-w","article-title":"Osteoarthritis: A narrative review of molecular approaches to disease management","volume":"25","author":"Salman","year":"2023","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.14336\/AD.2019.1116","article-title":"Infrapatellar Fat Pad and Knee Osteoarthritis","volume":"11","author":"Zeng","year":"2020","journal-title":"Aging Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fontanella, C.G., Belluzzi, E., Pozzuoli, A., Scioni, M., Olivotto, E., Reale, D., Ruggieri, P., De Caro, R., Ramonda, R., and Carniel, E.L. (2022). Exploring Anatomo-Morphometric Characteristics of Infrapatellar, Suprapatellar Fat Pad, and Knee Ligaments in Osteoarthritis Compared to Post-Traumatic Lesions. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061369"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rim, Y.A., and Ju, J.H. (2020). The Role of Fibrosis in Osteoarthritis Progression. Life, 11.","DOI":"10.3390\/life11010003"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Molnar, V., Mati\u0161i\u0107, V., Kodvanj, I., Bjelica, R., Jele\u010d, \u017d., Hudetz, D., Rod, E., \u010cukelj, F., Vrdoljak, T., and Vidovi\u0107, D. (2021). Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179208"},{"key":"ref_10","first-page":"959","article-title":"Warming moxibustion attenuates inflammation and cartilage degradation in experimental rabbit knee osteoarthriti","volume":"41","author":"Liu","year":"2021","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R5","DOI":"10.1186\/ar4133","article-title":"MMP13 is a critical target gene during the progression of osteoarthritis","volume":"15","author":"Wang","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","article-title":"Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis","volume":"12","author":"Robinson","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis","volume":"7","author":"Kapoor","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","first-page":"s237","article-title":"The role of cytokines in osteoarthritis pathophysiology","volume":"39","author":"Fernandes","year":"2002","journal-title":"Biorheology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/S0140-6736(23)01726-9","article-title":"Inflammation is a relevant treatment target in osteoarthritis","volume":"402","author":"Kloppenburg","year":"2023","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.4049\/jimmunol.165.5.2719","article-title":"TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: Involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1\/2 pathway","volume":"165","author":"Chen","year":"2000","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.bbrc.2010.09.095","article-title":"Analysis of isoform specific ERK signaling on the effects of interleukin-1\u03b2 on COX-2 expression and PGE2 production in human chondrocytes","volume":"402","author":"Wang","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/rheumatology\/39.10.1095","article-title":"The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: A randomized placebo-controlled trial","volume":"39","author":"Scott","year":"2000","journal-title":"Rheumatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1016\/S0140-6736(17)31744-0","article-title":"Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: A network meta-analysis","volume":"390","author":"Reichenbach","year":"2017","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.semarthrit.2015.11.010","article-title":"A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting","volume":"45","author":"Cooper","year":"2016","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.semarthrit.2014.05.014","article-title":"An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: A report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)","volume":"44","author":"Cooper","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_22","first-page":"13","article-title":"Intra-articular injections for the treatment of osteoarthritis: Focus on the clinical use of hyaluronic acid","volume":"11","author":"Iannitti","year":"2011","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"c7086","DOI":"10.1136\/bmj.c7086","article-title":"Cardiovascular safety of non-steroidal anti-inflammatory drugs: Network meta-analysis","volume":"342","author":"Trelle","year":"2011","journal-title":"BMJ"},{"key":"ref_24","first-page":"31","article-title":"Effectiveness and utility of hyaluronic acid in osteoarthritis","volume":"12","author":"Migliore","year":"2015","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yasin, A., Ren, Y., Li, J., Sheng, Y., Cao, C., and Zhang, K. (2022). Advances in Hyaluronic Acid for Biomedical Applications. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.910290"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Michalczyk, M., Humeniuk, E., Adamczuk, G., and Korga-Plewko, A. (2022). Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010103"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.18433\/J3K89D","article-title":"Hyaluronic acid and wound healing","volume":"18","author":"Neuman","year":"2015","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"622","DOI":"10.12688\/f1000research.6885.1","article-title":"Viscoelastic Properties of Hyaluronan in Physiological Conditions","volume":"4","author":"Cowman","year":"2015","journal-title":"F1000Res"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Iaconisi, G.N., Lunetti, P., Gallo, N., Cappello, A.R., Fiermonte, G., Dolce, V., and Capobianco, L. (2023). Hyaluronic Acid: A Powerful Biomolecule with Wide-Ranging Applications\u2014A Comprehensive Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210296"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/jbio.201100128","article-title":"Microrheology of human synovial fluid of arthritis patients studied by diffusing wave spectroscopy","volume":"5","author":"Chen","year":"2012","journal-title":"J. Biophotonics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1177\/0363546515609599","article-title":"Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee","volume":"44","author":"Altman","year":"2016","journal-title":"Am. J. Sports Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Altman, R.D., Manjoo, A., Fierlinger, A., Niazi, F., and Nicholls, M. (2015). The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: A systematic review. BMC Musculoskelet. Disord., 16.","DOI":"10.1186\/s12891-015-0775-z"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00167-009-1039-y","article-title":"Efficacy of intra-articular polynucleotides in the treatment of knee osteoarthritis: A randomized, double-blind clinical trial","volume":"18","author":"Vanelli","year":"2010","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_34","first-page":"543","article-title":"Intrarticular treatment of osteoartropaty knee with polynucleotides: A pilot study with medium-term follow-up","volume":"27","author":"Saggini","year":"2013","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.knee.2014.02.010","article-title":"A randomized double-blind clinical trial on the treatment of knee osteoarthritis: The efficacy of polynucleotides compared to standard hyaluronian viscosupplementation","volume":"21","author":"Giarratana","year":"2014","journal-title":"Knee"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Kim, Y.N., Lee, Y.J., Sim, S.E., Ko, Y.R., Shim, J.W., Lee, K.S., Joo, M., and Park, H.J. (2021). Pilot Study to Evaluate the Efficacy of Polynucleotide Sodium Compared to Sodium Hyaluronate and Crosslinked Sodium Hyaluronate in Patients with Knee Osteoarthritis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10051138"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9419","DOI":"10.1038\/s41598-023-35982-z","article-title":"A randomized controlled trial for comparing efficacy and safety between intraarticular polynucleotide and hyaluronic acid for knee osteoarthritis treatment","volume":"13","author":"Kim","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40902-016-0053-5","article-title":"Histologic study of bone-forming capacity on polydeoxyribonucleotide combined with demineralized dentin matrix","volume":"38","author":"Kim","year":"2016","journal-title":"Maxillofac. Plast. Reconstr. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1002\/jcp.25663","article-title":"Polydeoxyribonucleotides (PDRNs) from Skin to Musculoskeletal Tissue Regeneration via Adenosine A","volume":"232","author":"Veronesi","year":"2017","journal-title":"J. Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1002\/art.30538","article-title":"Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A2A receptor","volume":"63","author":"Bitto","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/JSM.0000000000000569","article-title":"Efficacy of Intra-Articular Polynucleotides Associated with Hyaluronic Acid versus Hyaluronic Acid Alone in the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Controlled Clinical Trial","volume":"30","author":"Dallari","year":"2020","journal-title":"Clin. J. Sport. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jang, J.Y., Kim, J.H., Kim, M.W., Kim, S.H., and Yong, S.Y. (2022). Study of the Efficacy of Artificial Intelligence Algorithm-Based Analysis of the Functional and Anatomical Improvement in Polynucleotide Treatment in Knee Osteoarthritis Patients: A Prospective Case Series. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102845"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Stagni, C., Rocchi, M., Mazzotta, A., Del Piccolo, N., Rani, N., Govoni, M., Vivarelli, L., Veronesi, F., Fini, M., and Dallari, D. (2021). Randomised, double-blind comparison of a fixed co-formulation of intra-articular polynucleotides and hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis: Two-year follow-up. BMC Musculoskelet. Disord., 22.","DOI":"10.1186\/s12891-021-04648-0"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bone.2005.08.007","article-title":"Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis","volume":"38","author":"Hayami","year":"2006","journal-title":"Bone"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Testa, G., Giardina, S.M.C., Culmone, A., Vescio, A., Turchetta, M., Cannav\u00f2, S., and Pavone, V. (2021). Intra-Articular Injections in Knee Osteoarthritis: A Review of Literature. J. Funct. Morphol. Kinesiol., 6.","DOI":"10.3390\/jfmk6010015"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.joca.2008.11.013","article-title":"Intra-articular injections of hyaluronan solutions of different elastoviscosity reduce nociceptive nerve activity in a model of osteoarthritic knee joint of the guinea pig","volume":"17","author":"Gomis","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/j.joca.2010.05.030","article-title":"The OARSI histopathology initiative\u2013recommendations for histological assessments of osteoarthritis in the rat","volume":"18","author":"Gerwin","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.30802\/AALAS-CM-21-000043","article-title":"Mouse Models of Osteoarthritis: A Summary of Models and Outcomes Assessment","volume":"72","author":"Drevet","year":"2022","journal-title":"Comp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1177\/0023677219867715","article-title":"Factors affecting the reliability of behavioral assessments for rodent osteoarthritis models","volume":"54","author":"Jacobs","year":"2020","journal-title":"Lab. Anim."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4196\/kjpp.2018.22.2.163","article-title":"Effects of salmon DNA fraction","volume":"22","author":"Ra","year":"2018","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/jor.23671","article-title":"Chemokine receptor-7 (CCR7) deficiency leads to delayed development of joint damage and functional deficits in a murine model of osteoarthritis","volume":"36","author":"Sambamurthy","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20602","DOI":"10.1073\/pnas.1209294110","article-title":"CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis","volume":"109","author":"Miller","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/j.joca.2013.06.016","article-title":"Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model","volume":"21","author":"Ruan","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15271","DOI":"10.1038\/s41598-020-72227-9","article-title":"Nociceptive mechanisms driving pain in a post-traumatic osteoarthritis mouse model","volume":"10","author":"Alves","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.pbb.2012.12.013","article-title":"Effect of iNOS inhibitor S-methylisothiourea in monosodium iodoacetate-induced osteoathritic pain: Implication for osteoarthritis therapy","volume":"103","author":"More","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3892\/etm.2020.9294","article-title":"Impairment in locomotor activity as an objective measure of pain and analgesia in a rat model of osteoarthritis","volume":"20","author":"Alsalem","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10753-017-0722-2","article-title":"Anti-inflammatory Effect of DNA Polymeric Molecules in a Cell Model of Osteoarthritis","volume":"41","author":"Baek","year":"2018","journal-title":"Inflammation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1002\/jor.25245","article-title":"Assessment of osteoarthritis functional outcomes and intra-articular injection volume in the rat anterior cruciate ligament transection model","volume":"40","author":"Wang","year":"2022","journal-title":"J. Orthop. Res."},{"key":"ref_59","first-page":"232","article-title":"Protocatechuic acid attenuates anterior cruciate ligament transection-induced osteoarthritis by suppressing osteoclastogenesis","volume":"19","author":"Zhang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sugasawa, T., Kuji, T., Aoki, K., Yanazawa, K., Takenouchi, A., Watanabe, M., Tome, Y., Takeuchi, Y., Aita, Y., and Yahagi, N. (2020). Characterization of Osteoarthritis in a Medial Meniscectomy-Induced Animal Model Using Contrast-Enhanced X-ray Microtomography. Biomedicines, 8.","DOI":"10.20944\/preprints202002.0106.v1"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.3892\/etm.2017.4849","article-title":"Evaluation of the chondroprotective action of N-acetylglucosamine in a rat experimental osteoarthritis model","volume":"14","author":"Kubomura","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"pdb.prot4986","DOI":"10.1101\/pdb.prot4986","article-title":"Hematoxylin and eosin staining of tissue and cell sections","volume":"2008","author":"Fischer","year":"2008","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.joca.2007.04.017","article-title":"Reliability, reproducibility and variability of the traditional Histologic\/Histochemical Grading System vs the new OARSI Osteoarthritis Cartilage Histopathology Assessment System","volume":"15","author":"Custers","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_64","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:51:56Z","timestamp":1760104316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031714"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031714","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,30]]}}}