Novel Insights into the Pathogenesis of Osteoarthritis.

Abstract Osteoarthritis represents the most frequently diagnosed condition of the musculoskeletal system and accounts for a high amount of direct and indirect socioeconomic costs worldwide. While for rheumatoid arthritis much progress has been made in the past decades both in understanding its pathogenesis and in creating novel therapies, the pathophysiology of osteoarthritis still holds several secrets to be unraveled in the near future in order to also allow for the development of effective novel pharmacotherapeutical options. Though first categorized as a joint disorder being primarily non-inflammatory in nature for a long period of time with research focused on biomechanic aspects and imbalanced wear and tear, recent evidence including immunological processes helped to refine disease interpretation. Thus, showing true inflammatory characteristics that clinically emerge as synovitis, osteoarthritis is nowadays recognized to include signs of inflammation that at least histologically may sometimes be indistinguishable from rheumatoid synovial infiltration. Although this was known already more than 25 years ago, efforts made in solving pathophysiologic key issues did not succeed sufficiently. This review is thought to summarize elementary pathogenic aspects including genetic predisposition and epigenetic regulation and highlights important central innate but also putative adaptive immunological mechanisms today generally accepted to drive inflammation and tissue destruction in osteoarthritis.