The effects of leptin hormone are mediated by interactions with several phy
siological regulatory systems and the cytokine network, and by targeting ce
lls directly. The leptin receptor is a member of the class I cytokine recep
tor family, and its signal transduction. resembles that induced by many cyt
okines. 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 detecte
d 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. Chondr
ocytes stimulated with leptin exhibited an increased proliferation and an e
nhanced synthesis of extracellular matrix (proteoglycans and collagen). The
se results indicate that leptin affects cartilage generation directly, whic
h is a novel role for leptin in skeletal growth and development. (C) 2001 A
cademic Press.