Departmental Papers (Dental)

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Journal Article

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Article number e72645




Transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-β1 and TGF-β2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-β with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-β2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-β2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-β administration in vivo is associated with greater bone formation than high-dose TGF-β administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-β activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-β compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders. © 2013 Tian et al.


At the time of publication, author Chenshuang Li was affiliated with the Peking University School and Hospital of Stomatology. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.


Adult, Animals, Bone Development, Humans, Kinetics, Peptide Fragments, Phosphoproteins, Protein Binding, Surface Plasmon Resonance, Transforming Growth Factor beta, bone morphogenetic protein, phosphoprotein, phosphoprotein 24, transforming growth factor alpha, transforming growth factor beta, transforming growth factor beta1, transforming growth factor beta2, unclassified drug, article, binding affinity, bioassay, bone development, bone disease, bone growth, bone metabolism, bone remodeling, bone turnover, carboxy terminal sequence, down regulation, histopathology, in vivo study, ossification, protein binding, protein interaction, protein secretion, surface plasmon resonance



Date Posted: 09 February 2023

This document has been peer reviewed.