{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:06:53Z","timestamp":1783746413002,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,29]],"date-time":"2011-12-29T00:00:00Z","timestamp":1325116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The mitochondrion is known to be important to chondrocyte survival. This study was undertaken to analyze protein expression profiles in chondrocyte mitochondria that are affected by interleukin\u20101\u03b2 (IL\u20101\u03b2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Normal human chondrocytes were isolated from knee cartilage obtained at autopsy from subjects with no history of joint disease. Cells were incubated for 48 hours with or without IL\u20101\u03b2 (5 ng\/ml). Proteins were separated by 2\u2010dimensional electrophoresis and stained with Sypro Ruby, Coomassie brilliant blue, or silver. Qualitative and quantitative analyses were carried out using PDQuest software. Proteins were identified by mass spectrometry using matrix\u2010assisted laser desorption ionization\u2013time\u2010of\u2010flight\/time\u2010of\u2010flight technology. The proteomic results were validated by real\u2010time polymerase chain reaction, Western blotting, and microscopy. Nitric oxide (NO) was quantified using Griess reagent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Comparative analysis revealed differential expression of signal transduction proteins that regulate cytoskeleton, transcription, metabolic, and stress\u2010related pathways. In total extracts, dimethylarginine dimethylaminohydrolase 2 (DDAH\u20102) did not show any change in expression after stimulation with IL\u20101\u03b2. However, in mitochondrial extracts, DDAH\u20102 expression was significantly increased after exposure to IL\u20101\u03b2. Conventional immunofluorescence and confocal microscopy revealed the presence of DDAH\u20102 in the mitochondria of IL\u20101\u03b2\u2013stimulated chondrocytes. These results were reproducible in cartilage explants treated with IL\u20101\u03b2. In addition, we demonstrated that inhibition of the expression of DDAH\u20102, as well as interruption of its translocation to the mitochondria, reduced the NO production induced by IL\u20101\u03b2. DDAH\u20102 protein expression was higher in osteoarthritic (OA) cartilage than in normal cartilage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the present study, the presence of DDAH\u20102 in normal human chondrocytes and cartilage was identified for the first time. DDAH\u20102 could play an important role in IL\u20101\u03b2\u2013induced NO production and in OA pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30652","type":"journal-article","created":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T03:44:42Z","timestamp":1314848682000},"page":"204-212","source":"Crossref","is-referenced-by-count":14,"title":["Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial protein modulating nitric oxide synthesis in normal human 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