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Principal Investigator: Natalie Lynn Andras
Organization: OHIO STATE UNIVERSITY
Fiscal Year: 2024
Award: $54,774
Funding agency: National Institute of Dental and Craniofacial Research
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.
Terms: <21+ years old><Ablation><Address><Adhesions><Adult><Adult Human><Affect><Age><Alveolodental Ligament><Alveolodental Membrane><Autoregulation><Binding><Biology><Bite Force><Blood Serum><Body Tissues><Bone Resorption><Bone remodeling><Buccal Cavity><Buccal Cavity Head and Neck><Cavitas Oris><Cell Attachment><Cell Body><Cell-Matrix Adhesions><Cell-Matrix Junction><Cells><Cementoblast><Cementogenesis><Cementum><Cephalic><Clinical><Collagen><Complex><Coupled><Coupling><Cranial><Data><Defect><Dental Cementum><Dentition><Development><Disease><Disease Progression><Disorder><Ensure><Epithelial Cells><Epithelium><Exhibits><Extracellular Matrix Proteins><Future><Gene Expression><Genes><Gingiva><Gingival><Goals><Health><Height><Homeostasis><Hydroxyapatites><Impairment><Infection><Inflammation><Integrin Binding><Interpersonal Interaction><Interpersonal Relations><Invaded><KO mice><Knock-out Mice><Knockout Mice><Knowledge><Maps><Masticatory Force><Mice><Mice Mammals><Microbe><Modeling><Molecular><Molecular Interaction><Mouth><Murine><Mus><Neural Crest><Null Mouse><Occlusal Force><Oophorectomy><Oral><Oral cavity><Osteoblasts><Osteoclastic Bone Loss><Osteoclasts><Osteoporotic><Ovariectomy><Paradentium><Parodontosis><Patients><Perimenopausal Bone Loss><Periodontal Diseases><Periodontal Ligament><Periodontal Membrane><Periodontium><Phenotype><Physiological Homeostasis><Population><Post-Menopausal Osteoporosis><Post-Menopause><Post-menopausal Period><Postmenopausal Bone Loss><Postmenopausal Osteoporosis><Postmenopausal Period><Postmenopause><Process><Proteins><Research><Rodent Model><Role><Serum><Skeleton><Source><Symptoms><Testing><Therapeutic><Tissues><Tooth><Tooth Extraction><Tooth Loss><Tooth Supporting Structures><Tooth structure><United States><Work><adulthood><after menopause><ages><alveolar bone><alveolar supporting bone><bite strength><bone healing><bone metabolism><bone remodelling><bone sialoprotein><bone sialoprotein II><bone wound healing><craniofacial><craniofacies><developmental><edentulism><experiment><experimental research><experimental study><experiments><female gonadectomy><following menopause><healing><improved><insight><integrin bound><interpersonal relationship><maxilla alveolar process><mineralization><novel><osseous wound healing><past menopause><periodontal disorder><periodontium disease><periodontium disorder><post-menopausal><postmenopausal><postmenopausal status><prevent><preventing><repair><repaired><self esteem><skeletal tissue><skeletons><social role><socket wall><teeth>