OBJECTIVE: To investigate leptin's effect on cartilage metabolism and the pathophysiology of osteoarthritis (OA). METHODS: Messenger RNA (mRNA) expression and protein levels of leptin and leptin's receptor isoforms were measured by real-time reverse transcription-PCR and Western blot in osteoarthritic and normal cartilage. Osteoarthritic cartilage samples were obtained from two locations of the knee (n=11) and hip (n=6); from the main defective area (advanced OA) and from adjacent macroscopically and histological intact regions (minimal OA). Paired serum and synovial fluid (SF) leptin levels were measured. The effect of leptin was evaluated on chondrocyte proliferation, IL-1beta (interleukin-1beta), NO and metalloproteinases 9 and 13 (MMP-9, MMP-13) protein expression. RESULTS: Leptin's and leptin's receptor (Ob-Rb) expression levels were significantly increased in advanced OA cartilage compared to minimal. Leptin was significantly increased in SF than serum samples. Also, leptin had a detrimental effect on chondrocyte proliferation and induced IL-1beta production and MMP-9 and MMP-13 protein expression. Furthermore, leptin's mRNA expression in advanced OA cartilage was significantly correlated with BMI of the patients. CONCLUSION: The increased leptin levels in SF point toward a local effect of leptin in articular cartilage, while the observed intrajoint differences of leptin and Ob-Rb mRNA expression may be related to the grade of cartilage destruction. The observed production of IL-1beta, MMP-9 and MMP-13 by chondrocytes after leptin treatment indicates a pro-inflammatory and catabolic role of leptin on cartilage metabolism. Furthermore, the observed correlation of leptin's mRNA expression with BMI suggests that leptin may be a metabolic link between obesity and OA.
OBJECTIVE: To investigate leptin's effect on cartilage metabolism and the pathophysiology of osteoarthritis (OA). METHODS: Messenger RNA (mRNA) expression and protein levels of leptin and leptin's receptor isoforms were measured by real-time reverse transcription-PCR and Western blot in osteoarthritic and normal cartilage. Osteoarthritic cartilage samples were obtained from two locations of the knee (n=11) and hip (n=6); from the main defective area (advanced OA) and from adjacent macroscopically and histological intact regions (minimal OA). Paired serum and synovial fluid (SF) leptin levels were measured. The effect of leptin was evaluated on chondrocyte proliferation, IL-1beta (interleukin-1beta), NO and metalloproteinases 9 and 13 (MMP-9, MMP-13) protein expression. RESULTS:Leptin's and leptin's receptor (Ob-Rb) expression levels were significantly increased in advanced OA cartilage compared to minimal. Leptin was significantly increased in SF than serum samples. Also, leptin had a detrimental effect on chondrocyte proliferation and induced IL-1beta production and MMP-9 and MMP-13 protein expression. Furthermore, leptin's mRNA expression in advanced OA cartilage was significantly correlated with BMI of the patients. CONCLUSION: The increased leptin levels in SF point toward a local effect of leptin in articular cartilage, while the observed intrajoint differences of leptin and Ob-Rb mRNA expression may be related to the grade of cartilage destruction. The observed production of IL-1beta, MMP-9 and MMP-13 by chondrocytes after leptin treatment indicates a pro-inflammatory and catabolic role of leptin on cartilage metabolism. Furthermore, the observed correlation of leptin's mRNA expression with BMI suggests that leptin may be a metabolic link between obesity and OA.
Authors: Timothy M Griffin; Beverley Fermor; Janet L Huebner; Virginia B Kraus; Ramona M Rodriguiz; William C Wetsel; Li Cao; Lori A Setton; Farshid Guilak Journal: Arthritis Res Ther Date: 2010-07-06 Impact factor: 5.156