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Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways

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Abstract

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.

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Acknowledgments

This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Miri Ben Eliezer, Sackler Faculty of Medicine, Tel Aviv University, Israel. This research was supported by The Israel Science Foundation (grant No. 1014/03).

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Authors and Affiliations

  1. Felsenstein Medical Research Center, 14 Kaplan Street, Petach Tikva, 49202, Israel

    Miri Ben-Eliezer, Moshe Phillip & Galia Gat-Yablonski

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Miri Ben-Eliezer & Moshe Phillip

  3. Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, Petach Tikva, 49202, Israel

    Moshe Phillip & Galia Gat-Yablonski

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  1. Miri Ben-Eliezer
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  2. Moshe Phillip
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Correspondence to Moshe Phillip.

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Ben-Eliezer, M., Phillip, M. & Gat-Yablonski, G. Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways. Endocr 32, 235–244 (2007). https://doi.org/10.1007/s12020-007-9025-y

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  • DOI: https://doi.org/10.1007/s12020-007-9025-y

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