{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:07:10Z","timestamp":1792015630938,"version":"4.4.0"},"reference-count":161,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world\u2019s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.<\/jats:p>","DOI":"10.3390\/jcm10091938","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T10:53:29Z","timestamp":1619780009000},"page":"1938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-8285","authenticated-orcid":false,"given":"Susanne","family":"Gr\u00e4ssel","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB), Bio Park 1, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9354","authenticated-orcid":false,"given":"Frank","family":"Zaucke","sequence":"additional","affiliation":[{"name":"Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopedic University Hospital Friedrichsheim, 60528 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8612-4842","authenticated-orcid":false,"given":"Henning","family":"Madry","sequence":"additional","affiliation":[{"name":"Center of Experimental Orthopaedics, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Litwic, A., Edwards, M.H., Dennison, E.M., and Cooper, C. (2013). Epidemiology and burden of osteoarthritis. Br. Med. 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