Ben-Eliezer Miri, Phillip Moshe, Gat-Yablonski Galia
Felsenstein Medical Research Center, 14 Kaplan Street, Petach Tikva, 49202, Israel.
Endocrine. 2007 Oct;32(2):235-44. doi: 10.1007/s12020-007-9025-y. Epub 2007 Dec 14.
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.
瘦素作为一种饱腹感激素，已被发现会影响生长板软骨的发育。在本研究中，对一些在ATDC5软骨细胞系（一种软骨内成骨模型）中介导瘦素信号传导的信号转导途径进行了分析。为此，使用了实时PCR、蛋白质免疫印迹和免疫荧光技术。研究发现，瘦素能以时间和剂量依赖的方式增加ERK1/2、p38和STAT3的磷酸化水平。对STAT3或ERK1/2进行特异性抑制，但不抑制P38，可阻断瘦素对X型胶原mRNA水平的刺激作用。此外，瘦素诱导ERK1/2转位至细胞核，并诱导c-fos表达，表明该信号级联被完全激活。虽然瘦素能显著且迅速地增加JNK蛋白水平和c-jun mRNA水平，但未观察到瘦素诱导的JNK磷酸化现象。另外，在这些细胞中鉴定出了ERK5，但瘦素对其磷酸化水平或蛋白水平均无明显影响。该研究表明，瘦素对生长板软骨细胞的作用是通过ERK1/2和STAT3特异性介导的，而P38对于瘦素诱导的X型胶原表达并非必需。这是首次证明这些信号途径参与了瘦素诱导的生长过程。
