Leptin Acts as a Growth Factor on the Chondrocytes of Skeletal Growth Centers

Authors

  • Gila Maor,

    1. Department of Morphology Science, Rappaport Faculty of Medicine, Technion, Haifa, Israel
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  • Miri Rochwerger,

    1. Department of Morphology Science, Rappaport Faculty of Medicine, Technion, Haifa, Israel
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  • Yael Segev,

    1. Molecular Endocrine Laboratory, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Moshe Phillip M.D.

    Corresponding author
    1. Molecular Endocrine Laboratory, Ben-Gurion University of the Negev, Beer-Sheva, Israel
    2. Felsenstein Medical Research Center, Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
    • Schneider Children's Medical Center of Israel, Institute of Endocrinology and Diabetes, National Center for Childhood Diabetes, 14 Kaplan Street, Petah Tiqva 49202, Israel
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  • The authors have no conflict of interest

Abstract

Childhood obesity frequently is associated with an increase in height velocity and acceleration of epiphyseal growth plate maturation despite low levels of serum growth hormone (GH). In addition, obesity is associated with higher circulating levels of leptin, a 16-kDa protein that is secreted from the adipocytes. In this study, we evaluated the direct effect of leptin on the chondrocyte population of the skeletal growth centers in the mouse mandibular condyle, a model of endochondral ossification. We found that chondrocytes in the growth centers contain specific binding sites for leptin. Leptin, at a concentration of 0.5-1.0 μg/ml, stimulated in a dose-dependent manner the width of the chondroprogenitor zone (up to 64%), whereas higher concentrations had an inhibitory effect. Leptin induction of both proliferation and differentiation activities in the mandibular condyle was confirmed by our findings of an increase in bromodeoxyuridine (BrdU) incorporation into DNA and in (acidic) Alcian blue (AB) staining of the cartilaginous matrix. Leptin also increased the abundance of the insulin-like growth factor (IGF) I receptor and IGF-I receptor messenger RNA (mRNA) within the chondrocytes and the progenitor cell population. Our results indicate that leptin acts as a skeletal growth factor with a direct peripheral effect on skeletal growth centers. Some of its effects on the growing bone may be mediated by the IGF system via regulation of IGF-I receptor expression. We speculate that the high circulating levels of leptin in obese children might contribute to their growth.

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