Leptin plays a catabolic role on articular cartilage. 2010

Jia-peng Bao, and Wei-ping Chen, and Jie Feng, and Peng-fei Hu, and Zhong-li Shi, and Li-dong Wu
Department of Orthopedics Surgery, The Second Hospital of Medical College, Zhejiang University College of Medicine, JieFang Road 88#, 310009, Hangzhou, People's Republic of China.

Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA.

UI MeSH Term Description Entries
D008297 Male Males
D011348 Procollagen N-Endopeptidase An extracellular endopeptidase which excises a block of peptides at the amino terminal, nonhelical region of the procollagen molecule with the formation of collagen. Absence or deficiency of the enzyme causes accumulation of procollagen which results in the inherited connective tissue disorder--dermatosparaxis. EC 3.4.24.14. Procollagen Peptidase,Procollagen N-Proteinase,Procollagen N Endopeptidase,Procollagen N Proteinase
D011509 Proteoglycans Glycoproteins which have a very high polysaccharide content. Proteoglycan,Proteoglycan Type H
D002358 Cartilage, Articular A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact. Articular Cartilage,Articular Cartilages,Cartilages, Articular
D002402 Cathepsin D An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000071116 ADAMTS5 Protein An ADAMTS protease that contains two C-terminal thrombospondin (TS) motifs. It functions primarily as an aggrecanase, cleaving AGGRECAN in CARTILAGE, and may be involved in the destruction of aggrecan in ARTHRITIS. A Disintegrin And Metalloproteinase With Thrombospondin Motifs 5 Protein,ADAMTS-5 Protein,ADAMTS11 Protein,ADAMTS5 Protease,Aggrecanase-2,ADAMTS 5 Protein,Aggrecanase 2
D000071121 ADAMTS4 Protein An ADAMTS protease similar to ADAMTS5 PROTEIN. It contains a single C-terminal thrombospondin (TS) motif and cleaves AGGRECAN in CARTILAGE. It may also be involved in the destruction of aggrecan in ARTHRITIS. A Disintegrin And Metalloproteinase With Thrombospondin Motifs 4 Protein,ADAMTS-4 Protein,Aggrecanase-1,ADAMTS 4 Protein,Aggrecanase 1
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014176 Protein Biosynthesis The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS. Genetic Translation,Peptide Biosynthesis, Ribosomal,Protein Translation,Translation, Genetic,Protein Biosynthesis, Ribosomal,Protein Synthesis, Ribosomal,Ribosomal Peptide Biosynthesis,mRNA Translation,Biosynthesis, Protein,Biosynthesis, Ribosomal Peptide,Biosynthesis, Ribosomal Protein,Genetic Translations,Ribosomal Protein Biosynthesis,Ribosomal Protein Synthesis,Synthesis, Ribosomal Protein,Translation, Protein,Translation, mRNA,mRNA Translations

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