Differential expression of leptin and leptin's receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism

被引:238
作者
Simopoulou, T.
Malizos, K. N.
Iliopoulos, D.
Stefanou, N.
Papatheodorou, L.
Loannou, M.
Tsezou, A.
机构
[1] Univ Thessalia, Sch Med, Dept Biol, Larisa 41222, Greece
[2] Univ Thessalia, Sch Med, Dept Orthopaed, Larisa, Greece
[3] Inst Biomed Res & Technol, Larisa, Greece
[4] Univ Thessalia, Sch Med, Dept Pathol, Larisa, Greece
[5] Univ Thessalia, Sch Med, Lab Cytogenet & Med Genet, Larisa, Greece
关键词
leptin; leptin receptor; cartilage; osteoarthritis; metabolism;
D O I
10.1016/j.joca.2007.01.018
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
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-1 beta (interleukin-1 beta), 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-1 beta 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-1 beta, 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. (c) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:872 / 883
页数:12
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