Leptin induces terminal differentiation of rat annulus fibrosus cells via activation of MAPK signaling.

Both leptin and its receptor are expressed in rat annulus fibrosus (AF) cells. However, little is known about their role and mechanism during disc degeneration. The mitogen activating protein kinase (MAPK) pathway which mediates leptin-induced terminal differentiation of rat AF cells was analyzed using PCR, Western-blot and immunocytochemistry. It was found that leptin-induced AF cells terminal differentiation, which may be attributed to upregulated p38 and ERK1/2 phosphorylation, however, JNK phosphorylation was not observed. Specific inhibitors of p38 or ERK1/2, but not JNK, could inhibit the stimulative activity of leptin on collagen X and MMP-13 protein levels. This study, for the first time, shows that the MAPK pathway, especially p38 and ERK1/2 signaling, plays a distinct role in leptin-induced AF cells terminal differentiation.