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Journal of Histochemistry and Cytochemistry, Vol. 50, 159-170, February 2002, Copyright © 2002, The Histochemical Society, Inc.

ARTICLE

Potential Role of Leptin in Endochondral Ossification

Keiko Kumea, Kazuhito Satomuraa, Sachiko Nishishoa, Eiichiro Kitaokaa, Kouji Yamanouchia, Satoru Tobiumea, and Masaru Nagayamaa
a First Department of Oral and Maxillofacial Surgery, School of Dentistry, The University of Tokushima, Tokushima, Japan

Correspondence to: Kazuhito Satomura, First Dept. of Oral and Maxillofacial Surgery, School of Dentistry, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. E-mail: satomura@dent.tokushima-u.ac.jp

Leptin, a 16-kD circulating hormone secreted mainly by white adipose tissue, is a product of the obese (ob) gene. Leptin acts on human marrow stromal cells to enhance differentiation into osteoblasts and inhibit differentiation into adipocytes. Leptin also inhibits bone formation through a hypothalamic relay. To obtain a better understanding of the potential role of leptin in bone formation, the localization of leptin in endochondral ossification was examined immunohistochemically. High expression of leptin was identified in hypertrophic chondrocytes in the vicinity of capillary blood vessels invading hypertrophic cartilage and in a number of osteoblasts of the primary spongiosa beneath the growth plate. The hypertrophic chondrocytes far from the blood vessels were negative for leptin. Moreover, we detected the production and secretion of leptin by a mouse osteoblast cell line (MC3T3-E1) and a mouse chondrocyte cell line (MCC-5) by RT-PCR, immunocytochemistry, and Western blotting. Leptin enhanced the proliferation, migration, tube formation, and matrix metalloproteinase-2 (MMP-2) activity of human endothelial cells (HUVECs) in vitro. These findings suggest the possibility that leptin exerts its influence on endochondral ossification by regulating angiogenesis. (J Histochem Cytochem 50:159–169, 2002)

Key Words: leptin, endochondral ossification, chondrocyte, osteoblast, endothelial cell, angiogenesis


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