HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wu, Y. Articles by Madri, J. A. Search for Related Content PubMed PubMed Citation Articles by Wu, Y. Articles by Madri, J. A.

Bone Marrow Monocyte PECAM-1 Deficiency Elicits Increased Osteoclastogenesis Resulting in Trabecular Bone Loss¹

Department of Pathology, Yale University School of Medicine, New Haven, CT 06520

In our investigations of the bone marrow (BM) of PECAM-1 null (knockout, KO) mice, we observed that the trabecular bone volume and number of trabeculae were significantly reduced in femural and tibial long bones. Further studies in vitro revealed increased numbers and size of osteoclasts, enhanced bone resorption on dentin substrates, and hypersensitivity to macrophage CSF and receptor activator of NF-B ligand in BM-derived osteoclast precursor cultures from KO mice. Associations among PECAM-1, Syk, and SHP-1 were found in wild-type BM monocyte derived osteoclast-like cells. The absence of PECAM-1 and SHP-1 interactions in the KO cells leads to the dysregulation of Syk kinases and/or phosphatases, possibly SHP-1. Indeed, KO derived osteoclast-like cells exhibited increased Syk tyrosine phosphorylation levels compared with WT cells. Lastly, WT mice engrafted with marrow from KO kindred showed loss of trabecular bone analogous to KO mice, consistent with increased osteoclastogenesis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported, in part, by United States Public Health Service Grants R37-HL28373 and R01-HL50518 (to J.A.M.) and a Reed Foundation Fellowship (to Y.W.).

² Address correspondence and reprint requests to Dr. Joseph A. Madri, Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520. E-mail address: joseph.Madri{at}yale.edu

³ Abbreviations used in this paper: SHP, Src homology phosphatase; KO, knockout; M-CSF, macrophage CSF; RANKL, receptor activator of NF-B ligand; FcR, Fc receptor common subunit; WT, wild type; BM, bone marrow; YCCMD, Yale Core Center for Musculoskeletal Disorders; TRAP, tartrate resistant acid phosphatase.