Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways.
Leptin, the satiety hormone, has been found to affect growth-plate cartilage development. In the present study, some of the signal transduction pathways that mediate leptin signaling in the ATDC5 chondrogenic cell-line, a model for endochondral ossification, were analyzed. For this purpose, real-time PCR, Western blots and immunofluorescence techniques were used. It was found that leptin increased phosphorylation of ERK1/2, p38, and STAT3 in a time- and dose-dependent manner. Specific inhibition of STAT3 or ERK1/2, but not of P38, blocked the stimulatory effect of leptin on type X collagen mRNA levels. Moreover, leptin induced the translocation of ERK1/2 into the nucleus, as well as c-fos expression, indicating full activation of this cascade. Leptin-induced JNK phosphorylation was not observed, although leptin significantly and rapidly increased JNK protein levels and c-jun mRNA levels. In addition, ERK5 was identified in these cells, but there was no apparent effect of leptin on either its phosphorylation or protein level. The study indicates that the effects of leptin on growth-plate chondrocytes are specifically mediated through ERK1/2 and STAT3, while P38 is not essential for leptin-induced type X collagen expression. This is the first demonstration that these pathways are involved in leptin-induced growth.
Ben-Eliezer
Miri
M
Felsenstein Medical Research Center, 14 Kaplan Street, Petach Tikva, 49202, Israel.
Phillip
Moshe
M
Gat-Yablonski
Galia
G
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects; D024121:Collagen Type X / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053612:Janus Kinases / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D024121:Collagen Type X; D020738:Leptin; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053612:Janus Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases