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Endocrinology Vol. 142, No. 1 430-436
Copyright © 2001 by The Endocrine Society

ARTICLES

Regulation of Growth Plate Chondrogenesis by Bone Morphogenetic Protein-21

Francesco De Luca, Kevin M. Barnes, Jennifer A. Uyeda, Stacy De-Levi, Veronica Abad, Teresa Palese, Veronica Mericq and Jeffrey Baron

Division of Pediatric Endocrinology, Department of Pediatrics, University of Maryland School of Medicine (F.D.L., T.P.), Baltimore, Maryland 21201-1595; and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (K.M.B., J.A.U., S.D.-L., V.A., V.M., J.B.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Francesco De Luca, Division of Pediatric Endocrinology, 22 South Greene Street, Room N5E13, Baltimore, Maryland 21201-1595. E-mail: fdeluca{at}peds.umaryland.edu

Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates growth plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal growth. As the rate of longitudinal bone growth depends primarily on the rate of growth plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the growth plate, as assessed by [3H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by 35SO4 incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-2-mediated stimulatory effects were reversed by recombinant human Noggin, a glycoprotein that blocks BMP-2 action. In the absence of exogenous BMP-2, Noggin inhibited metatarsal longitudinal growth, chondrocyte proliferation, and chondrocyte hypertrophy, which suggests that endogenous BMPs stimulate longitudinal bone growth and chondrogenesis. We conclude that BMP-2 accelerates longitudinal bone growth by stimulating growth plate chondrocyte proliferation and chondrocyte hypertrophy.




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