Leptin synergizes with thyroid hormone signaling in promoting growth plate chondrocyte proliferation and terminal differentiation in vitro.

Leptin and thyroid hormone are two hormones that regulate energy balance through central signaling mechanisms. Recent studies in leptin-deficient ob/ob mice indicate that leptin also has peripheral effects in modulating the function of the growth plate, perhaps in terms of proliferation and differentiation enhancement. Thyroid hormone has been well-described as a potent stimulator of growth plate chondrocyte maturation. The objective of this study was therefore to investigate the interaction between leptin and thyroid hormone signaling in growth plate chondrocyte proliferation and terminal differentiation. Our in vitro data demonstrate that leptin synergistically functions with thyroid hormone through activation of both IGF-1/IGF1R signaling and Wnt/β-catenin signaling, two pathways that have been previously described as downstream effectors of thyroid hormone action. Leptin increases thyroid hormone receptor-α (TRα) expression and thyroid hormone receptor transcriptional activity. Thyroid hormone also activates leptin signaling in growth plate cells undergoing proliferation and hypertrophy. We conclude that leptin synergically interacts with thyroid hormone in promoting growth plate chondrocyte proliferation and terminal differentiation.