{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:32:39Z","timestamp":1790404359937,"version":"4.1.0"},"reference-count":186,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:00:00Z","timestamp":1615075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients.<\/jats:p>","DOI":"10.3390\/ijms22052697","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T20:20:43Z","timestamp":1615148443000},"page":"2697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["From Pathogenesis to Therapy in Knee Osteoarthritis: Bench-to-Bedside"],"prefix":"10.3390","volume":"22","author":[{"given":"Elena","family":"Rezu\u015f","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Physiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-4685","authenticated-orcid":false,"given":"Alexandra","family":"Burlui","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Physiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Cardoneanu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Physiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-867X","authenticated-orcid":false,"given":"Luana Andreea","family":"Macovei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Physiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-1999","authenticated-orcid":false,"given":"Bogdan Ionel","family":"Tamba","sequence":"additional","affiliation":[{"name":"Advanced Center for Research and Development in Experimental Medicine (CEMEX), \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700454 Ia\u015fi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian","family":"Rezu\u015f","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41584-018-0010-z","article-title":"The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA","volume":"14","author":"Roemer","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","first-page":"130","article-title":"The \u201celusive DMOAD\u201d: Aggrecanase inhibition from laboratory to clinic","volume":"37","author":"Malfait","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Castrogiovanni, P., Di Rosa, M., Ravalli, S., Castorina, A., Guglielmino, C., Imbesi, R., Vecchio, M., Drago, F., Szychlinska, M.A., and Musumeci, G. (2019). 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