{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:34:36Z","timestamp":1790220876563,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institute of Health\/National Center for Complimentary and Integrative Health\/National Institute of Arthritis, Musculoskeletal and Skin Diseases","award":["RO1-AT-007373"],"award-info":[{"award-number":["RO1-AT-007373"]}]},{"name":"National Institute of Health\/National Center for Complimentary and Integrative Health\/National Institute of Arthritis, Musculoskeletal and Skin Diseases","award":["RO1-AT-005520"],"award-info":[{"award-number":["RO1-AT-005520"]}]},{"name":"National Institute of Health\/National Center for Complimentary and Integrative Health\/National Institute of Arthritis, Musculoskeletal and Skin Diseases","award":["RO1-AR-067056"],"award-info":[{"award-number":["RO1-AR-067056"]}]},{"name":"National Institute of Health\/National Center for Complimentary and Integrative Health\/National Institute of Arthritis, Musculoskeletal and Skin Diseases","award":["R21-AR-064890"],"award-info":[{"award-number":["R21-AR-064890"]}]},{"name":"Northeast Ohio Medical University"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      There is growing evidence in support of the involvement of inflammatory response in the pathogenesis of osteoarthritis (OA). Harpagoside, one of the bioactive components of\n                      <jats:italic>Harpagophytum procumbens (Hp)<\/jats:italic>\n                      , has been shown to possess anti\u2010inflammatory properties. Here we used an in vitro model of inflammation in OA to investigate the potential of harpagoside to suppress the production of inflammatory cytokines\/chemokines such as IL\u20106 and matrix degrading proteases. We further investigated the likely targets of harpagoside in primary human OA chondrocytes. OA chondrocytes were pre\u2010treated with harpagoside before stimulation with IL\u20101\u03b2. mRNA expression profile of 92 cytokines\/chemokines was determined using TaqMan Human Chemokine PCR Array. Expression levels of selected mRNAs were confirmed using TaqMan assays. Protein levels of IL\u20106 and MMP\u201013 were assayed by ELISA and immunoblotting. Total protein levels and phosphorylation of signaling proteins were determined by immunoblotting. Cellular localization of IL\u20106 and c\u2010Fos was performed by immunofluorescence and confocal microscopy. DNA binding activity of c\u2010FOS\/AP\u20101 was determined by ELISA. Harpagoside significantly altered the global chemokine expression profile in IL\u20101\u03b2\u2010stimulated OA chondrocytes. Expression of IL\u20106 was highly induced by IL\u20101\u03b2, which was significantly inhibited by pre\u2010treatment of OA chondrocytes with harpagoside. Harpagoside did not inhibit the IL\u20101\u03b2\u2010induced activation of NF\u2010\u03baB and C\/EBP\u03b2 transcription factors but suppressed the IL\u20101\u03b2\u2010triggered induction, phosphorylation, and DNA binding activity of c\u2010FOS, one of the main components of AP\u20101 transcription factors. Further, harpagoside significantly inhibited the expression of MMP\u201013 in OA chondrocytes under pathological conditions. siRNA\u2010mediated knockdown of IL\u20106 resulted in suppressed expression and secretion of MMP\u201013 directly linking the role of IL\u20106 with MMP\u201013 expression. Taken together, the present study suggests that harpagoside exerts a significant anti\u2010inflammatory effect by inhibiting the inflammatory stimuli mediated by suppressing c\u2010FOS\/AP\u20101 activity in OA chondrocytes under pathological conditions. \u00a9 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:311\u2013320, 2017.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jor.23262","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T17:46:58Z","timestamp":1460742418000},"page":"311-320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Harpagoside suppresses IL\u20106 expression in primary human osteoarthritis chondrocytes"],"prefix":"10.1002","volume":"35","author":[{"given":"Abdul","family":"Haseeb","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology North East Ohio Medical University 4209 State Route 44 Rootstown Ohio 44272"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Yunus","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology North East Ohio Medical University 4209 State Route 44 Rootstown Ohio 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