Age-related variations of leptin receptor expression in the growth plate of spine and limb: gender- and region-specific changes

Abstract

Leptin is a potent growth-stimulating factor of bone. The effects of leptin on bone growth differ significantly between axial and appendicular regions. Gender differences of leptin function have also been suggested in normal pubertal development. To explore the mechanisms underlying these effects, we investigated the spatial and temporal expressions of the active form of the leptin receptor (Ob-Rb) in the tibial and spinal growth plates of the female and male rats during postnatal development. The 1-, 4-, 7-, 12- and 16-week age stages are representative for early life, puberty and early adulthood after puberty, respectively. Quantitative real-time PCR was used for Ob-Rb mRNA examination and comparison. The spatial location of Ob-Rb was determined by immunohistochemical analysis. There were gender- and region-specific differences in Ob-Rb mRNA expression in the growth plate. Mainly cytoplasm staining of Ob-Rb immunoreactivity was observed in the spinal and tibial growth plate chondrocytes of both genders. Spatial differences of region- and gender-related Ob-Rb expression were not observed. Ob-Rb immunoreactivity was detected in the resting, proliferative and prehypertrophic chondrocytes in early life stage and during puberty. After puberty, staining was mainly located in the late proliferative and hypertrophic chondrocytes. The results of Ob-Rb HSCORE analysis were similar to those obtained from quantitative real-time PCR. Our study indicated direct effects on the chondrocytes of the growth plate in different development stages. The region-specific expression patterns of Ob-Rb gene might be one possible reason for contrasting phenotypes in limb and spine. Different Ob-Rb expression patterns might partly contribute to age- and gender- related differences in trabecular bone mass.