Efficient reconstruction of bone with high quality is critical for the success of dental implants, periodontal regeneration and treatments of bone defects in general. The goal of this study is to develop a means for efficient bone regeneration based on a unique function of a matrix proteoglycan in bone, biglycan (BGN). We have demonstrated that BGN accelerates osteoblast differentiation and matrix mineralization in vitro and that clones overexpressing BGN efficiently produced highly organized mineralized matrix upon their transplantation into immunodeficient mice. This function could be due in part to the unique ability of the BGN core protein to """"""""positively"""""""" modulate the functions of specific bone morphogenetic proteins (BMPs). Based on these and other preliminary data, we hypothesized that the specific domain of BGN core protein, i.e. the effector domain, exerts this unique function and is capable of promoting the formation of bone with high quality in vivo. To test this hypothesis, two specific aims are proposed:
in Aim 1, we will identify the effector domain by generating several BGN core protein-derived constructs and evaluating their capabilities to promote BMP-2 function, osteoblast differentiation and mineralization in vitro, and in Aim 2, we will test if the BGN/effector domain can promote bone formation in vivo employing a rat mandible defect model. The results of this study may provide insights into an effective, novel matrix-assisted bone formation and may help develop new therapeutic strategies for treating bone defects.

Public Health Relevance

A growing population of our aging society is suffering from craniofacial bone defects. Given the severely impaired quality of life and limitations of current treatments, development of new therapeutic strategies is of critical importance. Towards this end, this study will explore a novel approach to efficient and cost-effective craniofacial bone regeneration based on a unique function of bone matrix molecule, biglycan.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Lumelsky, Nadya L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Dentistry
Chapel Hill
United States
Zip Code
Miguez, P A; Terajima, M; Nagaoka, H et al. (2014) Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis. J Dent Res 93:406-11
Nagaoka, Hiroko; Nagaoka, Hideaki; Walter, Ricardo et al. (2014) Characterization of genipin-modified dentin collagen. Biomed Res Int 2014:702821
Terajima, Masahiko; Perdivara, Irina; Sricholpech, Marnisa et al. (2014) Glycosylation and cross-linking in bone type I collagen. J Biol Chem 289:22636-47
Nagaoka, Hideaki; Terajima, Masahiko; Yamada, Shizuka et al. (2014) Alfacalcidol enhances collagen quality in ovariectomized rat bones. J Orthop Res 32:1030-6
Sricholpech, Marnisa; Perdivara, Irina; Yokoyama, Megumi et al. (2012) Lysyl hydroxylase 3-mediated glucosylation in type I collagen: molecular loci and biological significance. J Biol Chem 287:22998-3009
Yamauchi, Mitsuo; Sricholpech, Marnisa (2012) Lysine post-translational modifications of collagen. Essays Biochem 52:113-33
Mochida, Yoshiyuki; Kaku, Masaru; Yoshida, Keiko et al. (2011) Podocan-like protein: a novel small leucine-rich repeat matrix protein in bone. Biochem Biophys Res Commun 410:333-8
Miguez, P A; Terajima, M; Nagaoka, H et al. (2011) Role of glycosaminoglycans of biglycan in BMP-2 signaling. Biochem Biophys Res Commun 405:262-6