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Despite their widespread use, knowledge of the specific molecular mechanisms of their action is limited. The aim of this work is to explore the utility of a pharmacoproteomic approach for the identification of specific molecules involved in the pharmacological effect of GS and CS.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Chondrocytes obtained from three healthy donors were treated with GS 10 mM and\/or CS 200 \u03bcg\/mL, and then stimulated with interleukin-1\u03b2 (IL-1\u03b2) 10 ng\/mL. Whole cell proteins were isolated 24 hours later and resolved by two-dimensional electrophoresis. The gels were stained with SYPRORuby. Modulated proteins were identified by matrix-assisted laser desorption\/ionization time-of-flight (MALDI-TOF\/TOF) mass spectrometry. Real-time PCR and Western blot analyses were performed to validate our results.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>A total of 31 different proteins were altered by GS or\/and CS treatment when compared to control. Regarding their predicted biological function, 35% of the proteins modulated by GS are involved in signal transduction pathways, 15% in redox and stress response, and 25% in protein synthesis and folding processes. Interestingly, CS affects mainly energy production (31%) and metabolic pathways (13%), decreasing the expression levels of ten proteins. The chaperone GRP78 was found to be remarkably increased by GS alone and in combination with CS, a fact that unveils a putative mechanism for the reported anti-inflammatory effect of GS in OA. On the other hand, the antioxidant enzyme superoxide dismutase 2 (SOD2) was significantly decreased by both drugs and synergistically by their combination, thus suggesting a drug-induced decrease of the oxidative stress caused by IL-1\u03b2 in chondrocytes.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>CS and GS differentially modulate the proteomic profile of human chondrocytes. This pharmacoproteomic approach unravels the complex intracellular mechanisms that are modulated by these drugs on IL1\u03b2-stimulated human articular chondrocytes.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar3077","type":"journal-article","created":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T18:14:20Z","timestamp":1279044860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes"],"prefix":"10.1186","volume":"12","author":[{"given":"Valentina","family":"Calamia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ruiz-Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Fern\u00e1ndez-Puente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Mateos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eul\u00e0lia","family":"Montell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Verg\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,7,13]]},"reference":[{"key":"2912_CR1","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1186\/ar2462","volume":"10","author":"F Berenbaum","year":"2008","unstructured":"Berenbaum F: New horizons and perspectives in the treatment of osteoarthritis. 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