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A Carboxy Terminal BMP/TGF‐β Binding Site in Secreted Phosphoprotein 24 kD Independently Affects BMP‐2 Activity
Author(s) -
Tian Haijun,
Li ChenShuang,
Zhao KeWei,
Wang Jeffrey C.,
Duarte M. Eugenia L.,
David Cynthia L.,
Phan Kevin,
Atti Elisa,
Brochmann Elsa J.,
Murray Samuel S.
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25023
Subject(s) - phosphoprotein , bone morphogenetic protein 7 , bone morphogenetic protein 10 , bone morphogenetic protein 2 , chemistry , microbiology and biotechnology , bone morphogenetic protein , transforming growth factor , cytokine , biochemistry , phosphorylation , biology , gene , immunology , in vitro
ABSTRACT Secreted phosphoprotein 24 kD (spp24) is a bone matrix protein isolated during attempts to identify osteogenic proteins. It is not osteogenic but performs other important roles in the regulation of bone metabolism, at least in part, by binding to and affecting the activity of members of the BMP/TGF‐β family of cytokines. Spp24 exists in a number of forms that preserve the N‐terminus and are truncated at the C‐terminus. The hypothesized cytokine binding domain is present within the cystatin domain which is preserved in all of the N‐terminal products. In this report, we describe a C‐terminal fragment that is distinct from the cystatin domain and which independently binds to BMP‐2 and TGF‐β. This fragment inhibited BMP‐2 activity in an ectopic bone forming assay. A shorter C‐terminal product did not inhibit BMP‐2 activity but improved bone quality induced by BMP‐2 and produced increased calcium deposition outside of bone. Spp24 has been used to develop several potential therapeutic proteins. These results provide more information on the function of spp24 and provide other materials that can be exploited for clinical interventions. J. Cell. Biochem. 116: 667–676, 2015. © 2014 Wiley Periodicals, Inc.