Leptin stimulates parathyroid hormone related peptide expression in the endochondral growth plate

We have previously shown that growth plate chondrocytes expressed the long form of leptin receptor, and that within the growth plate, leptin stimulated cell proliferation and differentiation and epiphyseal growth in a balanced manner. These three cell processes are known to be regulated by the interactions of parathyroid hormone-related peptide (PTHrP) and Indian hedgehog (Ihh) protein. The aim of the present study was to examine the effect of leptin on the PTHrP/Ihh feedback loop. The effect of leptin was investigated in vivo in pair-fed experiments in ICR mice, and ex vivo in mandibular condyle explants incubated with leptin. Immunohistochemistry and in situ hybridization showed that in the pair-fed in vivo system as well as in the organ culture, leptin increased the level of PTHrP and reduced that of Ihh. Leptin may affect chondrocyte proliferation and differentiation by activating the PTHrP/Ihh growth-restraining feedback loop in the postnatal growth plate.