Matrix-assisted Craniofacial Bone Regeneration

基质辅助颅面骨再生

• 批准号: 8197644
• 负责人: MITSUO YAMAUCHI
• 金额: $ 22.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197644
• 关键词: Aging; Bone Matrix; Bone Morphogenetic Proteins; Bone Regeneration; Core Protein; Data; Defect; Dental Implants; Development; Excision; Family; Glutathione S-Transferase; Glycosaminoglycans; Goals; Growth Factor; Health; Immunodeficient Mouse; In Vitro; Leucine; Mandible; Modeling; Natural regeneration; Operative Surgical Procedures; Osteogenesis; Population; Proteoglycan; Quality of life; Rattus; Societies; Testing; Transplantation; base; biglycan; bone; bone morphogenetic protein 2; bone morphogenetic protein 7; cost; cost effective; craniofacial; extracellular; in vivo; insight; member; mineralization; novel; novel strategies; novel therapeutics; osteoblast differentiation; overexpression; protein function; public health relevance; reconstruction; scaffold; success; therapy development

DESCRIPTION (provided by applicant): 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.

描述(由申请人提供)：高质量的高效骨重建对于牙种植体的成功、牙周再生和骨缺陷的治疗至关重要。本研究的目的是开发一种基于骨中基质蛋白多糖的独特功能的高效骨再生方法，即BGN。我们已经证明，BGN在体外可以促进成骨细胞分化和基质矿化，并且高表达BGN的克隆移植到免疫缺陷小鼠体内后，可以有效地产生高度组织化的矿化基质。这一功能可能部分归因于BGN核心蛋白“正向”调节特定骨形态发生蛋白(BMPs)功能的独特能力。基于这些和其他初步数据，我们假设BGN核心蛋白的特定结构域，即效应结构域，发挥着这一独特的功能，并能够促进体内高质量的骨形成。为了验证这一假设，我们提出了两个具体的目标：在目标1中，我们将通过生成几个BGN核心蛋白衍生的构建体并评估它们在体外促进BMP-2功能、成骨细胞分化和矿化的能力来确定效应域，在目标2中，我们将使用大鼠下颌骨缺损模型来测试BGN/效应域是否能够促进体内骨形成。这项研究的结果可能为一种有效的、新的基质辅助骨形成提供见解，并可能有助于开发治疗骨缺损的新治疗策略。 与公共健康相关：我们老龄化社会中不断增长的人口正在遭受颅面部骨缺陷的困扰。鉴于严重损害的生活质量和目前治疗的局限性，开发新的治疗策略至关重要。为此，本研究将基于骨基质分子Biglycan的独特功能，探索一种高效、经济的颅面骨再生新途径。

项目成果

Characterization of genipin-modified dentin collagen.

京尼平修饰的牙本质胶原蛋白的表征。

• DOI: 10.1155/2014/702821
• 发表时间: 2014
• 期刊: BioMed research international
• 作者: Nagaoka,Hiroko;Nagaoka,Hideaki;Walter,Ricardo;Boushell,LeeW;Miguez,PatriciaA;Burton,Andrew;Ritter,AndréV;Yamauchi,Mitsuo
• 通讯作者: Yamauchi,Mitsuo

Alfacalcidol enhances collagen quality in ovariectomized rat bones.

• DOI: 10.1002/jor.22642
• 发表时间: 2014-08
• 期刊: JOURNAL OF ORTHOPAEDIC RESEARCH
• 影响因子: 2.8
• 作者: Nagaoka, Hideaki;Terajima, Masahiko;Yamada, Shizuka;Azuma, Yoshiaki;Chida, Takayuki;Yamauchi, Mitsuo
• 通讯作者: Yamauchi, Mitsuo

Role of glycosaminoglycans of biglycan in BMP-2 signaling.

• DOI: 10.1016/j.bbrc.2011.01.022
• 发表时间: 2011-02-11
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Miguez PA;Terajima M;Nagaoka H;Mochida Y;Yamauchi M
• 通讯作者: Yamauchi M

Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function.

• DOI: 10.1038/s41598-018-25279-x
• 发表时间: 2018-05-04
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Jongwattanapisan P;Terajima M;Miguez PA;Querido W;Nagaoka H;Sumida N;Gurysh EG;Ainslie KM;Pleshko N;Perera L;Yamauchi M
• 通讯作者: Yamauchi M