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Leptin Acts as a Growth Factor on the Chondrocytes of Skeletal Growth Centers
Author(s) -
Maor Gila,
Rochwerger Miri,
Segev Yael,
Phillip Moshe
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.6.1034
Subject(s) - medicine , endocrinology , leptin , chondrocyte , leptin receptor , endochondral ossification , growth factor , biology , population , cartilage , insulin like growth factor , chemistry , receptor , obesity , anatomy , environmental health
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.