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Endocrinology Vol. 139, No. 12 5125-5134
Copyright © 1998 by The Endocrine Society

ARTICLES

LMP-1, A LIM-Domain Protein, Mediates BMP-6 Effects on Bone Formation

Scott D. Boden1, Yunshan Liu1, Gregory A. Hair1, Jill A. Helms, Diane Hu, Michele Racine, Mark S. Nanes and Louisa Titus

Emory University School of Medicine (S.D.B., Y.L., G.A.H., M.R.), Department of Orthopaedic Surgery, and Atlanta Veterans Affairs Medical Center, Decatur, Georgia 30033; Division of Endocrinology and Metabolism (F.L.T., M.S.N.), Emory University School of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, Georgia 30033; and University of California San Francisco School of Medicine (J.A.H., D.H.), Department of Orthopaedic Surgery, San Francisco, California 94143

Address all correspondence and requests for reprints to: Scott D. Boden, M.D., The Emory Spine Center, 2165 North Decatur Road, Decatur, Georgia 30033.

Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow stromal cells. We recently reported that glucocorticoid specifically induced bone morphogenetic protein-6 (BMP-6), a glycoprotein signaling molecule that is a multifunctional regulator of vertebrate development. In the present study, we used fetal rat secondary calvarial cultures to determine genes induced during early osteoblast differentiation as initiated by glucocorticoid treatment.

Glucocorticoid, and subsequently BMP-6, was found to induce a novel rat intracellular protein, LIM mineralization protein-1 (LMP-1), that in turn resulted in synthesis of one or more soluble factors that could induce de novo bone formation. Blocking expression of LMP-1 using antisense oligonucleotide prevented osteoblast differentiation in vitro. Overexpression of LMP-1 using a mammalian expression vector was sufficient to initiate de novo bone nodule formation in vitro and in sc implants in vivo. These data demonstrate that LMP-1 is an essential positive regulator of the osteoblast differentiation program as well as an important intermediate step in the BMP-6 signaling pathway.




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