Human articular chondrocytes express functional leptin receptors.
The effects of leptin hormone are mediated by interactions with several physiological regulatory systems and the cytokine network, and by targeting cells directly. The leptin receptor is a member of the class I cytokine receptor family, and its signal transduction resembles that induced by many cytokines. We demonstrated that serially cultured human articular chondrocytes possess the leptin receptor (Ob-R), and that this receptor was present on chondrocytes in native human cartilage. In cultured chondrocytes we detected mRNA for the functional isoform of leptin receptor (Ob-Rb or Ob-R(L)), and it was revealed that ligand binding resulted in phosphorylation of signal transducers and activators of transcription, namely STAT1 and STAT5. Chondrocytes stimulated with leptin exhibited an increased proliferation and an enhanced synthesis of extracellular matrix (proteoglycans and collagen). These results indicate that leptin affects cartilage generation directly, which is a novel role for leptin in skeletal growth and development.
Figenschau
Y
Y
Department of Immunology and Transfusion Medicine, University Hospital of Tromso, 9038 RiTø, Norway. yngve.figenschau@rito.no
Knutsen
G
G
Shahazeydi
S
S
Johansen
O
O
Sveinbjörnsson
B
B
D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000494:pharmacology*; D008894:Milk Proteins; D011509:Proteoglycans / Q000378:metabolism; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000032:analysis
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C515448:LEPR protein, human; D020738:Leptin; D008894:Milk Proteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D003094:Collagen