PMID- 22077999 OWN - NLM STAT- MEDLINE DCOM- 20121214 LR - 20220318 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 13 IP - 6 DP - 2011 TI - Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways. PG - R184 LID - 10.1186/ar3512 [doi] AB - INTRODUCTION: Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA). METHODS: Cartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated using Ahlback classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, that is, cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the time of surgery were cultured ex vivo, and the levels of adiponectin, nitric oxide (NO), IL-6, MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures. RESULTS: Plasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with the radiologically most severe OA (Ahlback grades 4 and 5) than in patients with less severe disease (Ahlback grades 1 to 3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, that is, COMP (r = 0.55, P = 0.001) and MMP-3 (r = 0.34, P = 0.046). Adiponectin was released by OA cartilage ex vivo, and it correlated positively with production of NO (r = 0.43, P = 0.012), IL-6 (r = 0.42, P = 0.018) and MMP-3 (r = 0.34, P = 0.051). Furthermore, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro in a mitogen-activated protein kinase (MAPK)-dependent manner. CONCLUSIONS: The findings of this study show that adiponectin is associated with, and possibly mediates, cartilage destruction in OA. FAU - Koskinen, Anna AU - Koskinen A AD - The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Medisiinarinkatu 3, Tampere, FI-33014, Finland. FAU - Juslin, Sami AU - Juslin S FAU - Nieminen, Riina AU - Nieminen R FAU - Moilanen, Teemu AU - Moilanen T FAU - Vuolteenaho, Katriina AU - Vuolteenaho K FAU - Moilanen, Eeva AU - Moilanen E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111111 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Adiponectin) RN - 0 (Biomarkers) RN - 0 (Cartilage Oligomeric Matrix Protein) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Flavonoids) RN - 0 (Glycoproteins) RN - 0 (Interleukin-6) RN - 0 (Matrilin Proteins) RN - 0 (TSP5 protein, human) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM CIN - Arthritis Res Ther. 2012;14(3):402. PMID: 22716456 MH - Adiponectin/blood/*metabolism/pharmacology MH - Aged MH - Biomarkers/blood MH - Blotting, Western MH - Cartilage/drug effects/*metabolism MH - Cartilage Oligomeric Matrix Protein MH - Cells, Cultured MH - Chondrocytes/cytology/drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Extracellular Matrix Proteins/blood/metabolism MH - Flavonoids/pharmacology MH - Glycoproteins/blood/metabolism MH - HEK293 Cells MH - Humans MH - Interleukin-6/metabolism MH - MAP Kinase Signaling System/drug effects MH - Male MH - Matrilin Proteins MH - Matrix Metalloproteinase 1/metabolism MH - Matrix Metalloproteinase 3/blood/metabolism MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Nitric Oxide/metabolism MH - Osteoarthritis/blood/*metabolism/pathology MH - Severity of Illness Index MH - Tissue Culture Techniques PMC - PMC3334633 EDAT- 2011/11/15 06:00 MHDA- 2012/12/15 06:00 PMCR- 2011/11/11 CRDT- 2011/11/15 06:00 PHST- 2011/08/24 00:00 [received] PHST- 2011/10/25 00:00 [revised] PHST- 2011/11/11 00:00 [accepted] PHST- 2011/11/15 06:00 [entrez] PHST- 2011/11/15 06:00 [pubmed] PHST- 2012/12/15 06:00 [medline] PHST- 2011/11/11 00:00 [pmc-release] AID - ar3512 [pii] AID - 10.1186/ar3512 [doi] PST - ppublish SO - Arthritis Res Ther. 2011;13(6):R184. doi: 10.1186/ar3512. Epub 2011 Nov 11.