The Role of Bone Sialoprotein in Modulating Periodontal Development and Repair

骨唾液酸蛋白在调节牙周发育和修复中的作用

• 批准号: 10752141
• 负责人: Natalie Lynn Andras
• 金额: $ 5.35万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752141
• 关键词: Ablation; Address; Adhesions; Adult; Affect; Age; Binding; Biology; Bite Force; Bone Resorption; Bone remodeling; Cell-Matrix Junction; Cells; Cementoblast; Cementogenesis; Cephalic; Clinical; Collagen; Complex; Coupled; Coupling; Data; Defect; Dental Cementum; Dentition; Development; Disease; Disease Progression; Ensure; Epithelial Cells; Epithelium; Exhibits; Extracellular Matrix Proteins; Future; Gene Expression; Genes; Gingiva; Goals; Health; Height; Homeostasis; Hydroxyapatites; Impairment; Infection; Inflammation; Integrin Binding; Interpersonal Relations; Invaded; Knockout Mice; Knowledge; Maps; Microbe; Modeling; Molecular; Mus; Neural Crest; Oral; Oral cavity; Osteoblasts; Osteoclasts; Osteoporotic; Ovariectomy; Patients; Periodontal Diseases; Periodontal Ligament; Periodontium; Phenotype; Population; Postmenopausal Osteoporosis; Postmenopause; Process; Proteins; Research; Rodent Model; Role; Serum; Skeleton; Source; Symptoms; Testing; Therapeutic; Tissues; Tooth Extraction; Tooth Loss; Tooth structure; United States; Work; alveolar bone; bone healing; bone metabolism; bone sialoprotein; craniofacial; edentulism; experimental study; healing; improved; insight; mineralization; novel; prevent; repaired; self esteem; skeletal tissue

Project Summary In the United States, 47% of adults 30 years or older are affected by periodontal disease, and this rate increases with age to 70% in adults 65 years or older. The periodontal complex, consisting of alveolar bone, cementum, gingiva, and the periodontal ligament (PDL), works to ensure proper tooth attachment and nourishment, distribute occlusal forces, maintain alveolar bone height, and protect the periodontium from invading microbes. Periodontal disease leads to the destruction of one or more of these tissues, which ultimately results in partial or total edentulism as well as reduced function of the masticatory complex, self- esteem, and interpersonal relationships. Most therapies are unpredictable as well as unsuccessful at repairing all three lost or damaged tissues. Bone sialoprotein (Ibsp gene; BSP protein) is a multifunctional, extracellular matrix protein found in mineralized tissues of the skeleton and dentition, including alveolar bone and cementum. Total knockout mice (Ibsp-/-) display reduced acellular cementum, hypomineralized alveolar bone, PDL detachment, severe alveolar bone resorption, tooth loss, and periodontal destruction. To date, nearly all studies on BSP focus on its roles in cranial and postcranial development. However, its dual functions in osteoblasts and osteoclasts also suggest an important role in the coupled process of bone remodeling; Ibsp-/- mice show dramatic defects in alveolar bone socket healing following molar extraction. While the importance of BSP in the periodontal complex is evident, its molecular functions remain unclear. We propose BSP is a key molecule in periodontal development, homeostasis, and repair. The outlined experiments will test our central hypothesis that BSP modulates periodontal development and repair through its functions in key cells for periodontal function: cementoblasts, osteoblasts, and osteoclasts. The overall objectives of this proposal are: 1.) define the origin of BSP and cementoblast lineage using conditional ablation of Ibsp from ectomesenchymal vs. epithelial cell populations; 2.) elucidate the role(s) of BSP in osteoblast and osteoclast function(s) in alveolar bone healing by conditionally ablating Ibsp from osteoblasts and osteoclasts; and 3.) determine the role of BSP in postmenopausal osteoporotic changes to bone metabolism using an ovariectomy (OVX) rodent model of postmenopausal osteoporosis. The knowledge gained from this proposal holds promise for the development of novel and reparative therapies of the periodontal complex. Successful completion of the proposed research will provide key insights into the function(s) of BSP in periodontal biology as well as diseases characterized by excessive osteoblast-osteoclast decoupling.

项目摘要 在美国，47%的30岁或以上的成年人受到牙周病的影响，这一比率 随着年龄的增长，65岁或65岁以上的成年人增加到70%。牙周复合体由牙槽骨组成， 牙骨质、牙龈和牙周韧带（PDL）的作用是确保牙齿正确附着， 营养，分配咬合力，保持牙槽骨高度，保护牙周组织免受 入侵的微生物牙周病导致这些组织中的一种或多种的破坏， 最终导致部分或全部牙缺失以及咀嚼复合体、自身 尊重和人际关系。大多数疗法是不可预测的，并且在修复方面是不成功的。 所有三个组织丢失或受损。骨唾液酸蛋白（Ibsp基因; BSP蛋白）是一种多功能的细胞外， 在骨骼和牙列的矿化组织中发现的基质蛋白，包括牙槽骨和 牙骨质。全基因敲除小鼠（Ibsp-/-）表现出减少的无细胞牙骨质，低矿化牙槽骨， 牙周膜脱离，严重的牙槽骨吸收，牙齿脱落和牙周破坏。到目前为止，几乎所有 对BSP的研究主要集中在其在颅和颅后发育中的作用。然而，它的双重功能在 成骨细胞和破骨细胞也提示在骨重建的耦合过程中起重要作用; Ibsp-/- 小鼠在磨牙拔除后牙槽骨窝愈合中表现出显著的缺陷。虽然重要的是 BSP在牙周复合体中的作用是明显的，其分子功能尚不清楚。我们提出BSP是一个关键 分子在牙周发育、稳态和修复中的作用。概述的实验将测试我们的中央 假设BSP通过其在关键细胞中的功能调节牙周发育和修复， 牙周功能：成牙骨质细胞、成骨细胞和破骨细胞。本提案的总体目标是： 1.）的人。通过条件性切除外胚间充质中的Ibsp来确定BSP和成牙骨质细胞谱系的起源 vs.上皮细胞群; 2.）阐明BSP在成骨细胞和破骨细胞功能中的作用， 通过从成骨细胞和破骨细胞有条件地消融Ibsp来实现牙槽骨愈合;以及3.）确定 用卵巢切除术（OVX）啮齿类动物研究BSP在绝经后骨代谢退行性变化中的作用 绝经后骨质疏松症模型。从这一建议中获得的知识为 开发牙周复合体的新型修复疗法。成功完成 拟议的研究将提供关键的洞察BSP在牙周生物学中的功能，以及 以过度的成骨细胞-破骨细胞分离为特征的疾病。