{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:10:48Z","timestamp":1789650648726,"version":"4.0.0"},"reference-count":94,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Anatomy"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by cartilage breakdown, inflammation, and subchondral bone remodeling. As research increasingly relies on physiologically relevant systems, advanced in\u00a0vitro models have become essential for exploring OA mechanisms and identifying therapeutic targets. This review synthesizes current developments in two\u2010dimensional (2D) and three\u2010dimensional (3D) in\u00a0vitro models used to investigate OA\u2010related signaling pathways and therapeutic strategies. This review aims to critically evaluate and compare two\u2010dimensional (2D) and three\u2010dimensional (3D) in\u00a0vitro OA models, with particular emphasis on their structural characteristics, signaling mechanisms, and translational relevance. Relevant literature published between January 2009 and January 2025 was examined across major scientific databases, including PubMed, Scopus, and Web of Science. Studies employing 2D or 3D in\u00a0vitro OA models to explore signaling mechanisms or therapeutic interventions were reviewed and integrated into a qualitative narrative synthesis. Across the analyzed literature, 3D models\u2014such as bioprinted constructs, organoids, microfluidic systems, and stem\u2010cell\u2013derived platforms\u2014were consistently reported to more closely replicate OA\u2010related structural, biochemical, and biomechanical processes than traditional 2D systems. These models facilitated deeper insights into key pathways, including NF\u2010\u03baB, Wnt\/\u03b2\u2010catenin, and TGF\u2010\u03b2 signaling. Emerging technologies such as joint\u2010on\u2010a\u2010chip systems and patient\u2010specific induced pluripotent stem cell (iPSC) platforms further enhance translational potential by enabling personalized disease modeling. Key signaling pathways identified across the included studies included NF\u2010\u03baB, Wnt\/\u03b2\u2010catenin, and TGF\u2010\u03b2 signaling, which were consistently associated with inflammatory responses, chondrocyte hypertrophy, and cartilage remodeling processes. Narrative synthesis of current evidence highlights the substantial progress made in 3D in\u00a0vitro OA modeling. By incorporating stem cells, bioprinting approaches, physiologically relevant matrix environments, and inflammatory stimuli, these platforms offer improved fidelity in mimicking joint physiology and OA progression. Collectively, they represent an important step toward more accurate drug testing and the development of personalized therapeutic strategies.<\/jats:p>","DOI":"10.1002\/ca.70137","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T06:20:48Z","timestamp":1777270848000},"page":"847-860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Targets and Signaling Mechanisms in\n                    <scp>2D<\/scp>\n                    and\n                    <scp>3D<\/scp>\n                    In\u00a0Vitro Models of Osteoarthritis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6255-4372","authenticated-orcid":false,"given":"Dineshwary","family":"Suresh","sequence":"first","affiliation":[{"name":"College of Medicine Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health  Dubai UAE"},{"name":"Faculty of Medicine, Health and Life Science Swansea University  Swansea Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7160-7510","authenticated-orcid":false,"given":"Kavitha","family":"Raja","sequence":"additional","affiliation":[{"name":"College of Medicine Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health  Dubai UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2735-0775","authenticated-orcid":false,"given":"Adam","family":"Eid","sequence":"additional","affiliation":[{"name":"College of Medicine Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health  Dubai UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1475-0561","authenticated-orcid":false,"given":"Ivan James","family":"Prithishkumar","sequence":"additional","affiliation":[{"name":"College of Medicine Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health  Dubai UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-2991","authenticated-orcid":false,"given":"Thomas","family":"Nau","sequence":"additional","affiliation":[{"name":"College of Medicine Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health  Dubai UAE"},{"name":"King's College London Dubai Hospital  Dubai UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0924-8796","authenticated-orcid":false,"given":"Nerissa","family":"Naidoo","sequence":"additional","affiliation":[{"name":"College of Medicine Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health  Dubai UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092319"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-00994-y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10091306"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11244011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2017.00076"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110452"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2019.100008"},{"key":"e_1_2_9_9_1","article-title":"Biomechanical Influence of Cartilage Homeostasis in Health and Disease","volume":"2011","author":"Bader D. 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