title: A carboxy terminal BMP/TGF-β binding site in secreted phosphoprotein 24 kD independently affects BMP-2 activity.
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.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, P.R. China; Department of Orthopaedic Surgery, University of California, Los Angeles, California, 90024.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: Chen-Shuang
authors.initials: CS
authors.lastname: Li
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Zhao
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.forename: M Eugenia L
authors.initials: ME
authors.lastname: Duarte
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: David
authors.forename: Kevin
authors.initials: K
authors.lastname: Phan
authors.forename: Elisa
authors.initials: E
authors.lastname: Atti
authors.forename: Elsa J
authors.initials: EJ
authors.lastname: Brochmann
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Murray
mesh_terms: D000818:Animals; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D010012:Osteogenesis; D010446:Peptide Fragments / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D010446:Peptide Fragments; D010750:Phosphoproteins; C551869:SPP2 protein, human; C000605935:SPP2 protein, mouse; D016212:Transforming Growth Factor beta; C091340:secreted phosphoprotein 24
keywords: BONE MORPHOGENETIC PROTEIN 2; BONE RESEARCH; SECRETED PHOSPHOPROTEIN 24 kD