# Functional domains of bone sialoprotein in dentoalveolar development and healing

> **NIH NIH F30** · OHIO STATE UNIVERSITY · 2021 · $43,436

## Abstract

Abstract:
Oral health is vital for overall health and quality of life, as exemplified by the importance of teeth in mastication,
speech, and esthetics, and by recent connections made between oral health and diabetes, heart disease,
preterm birth, and Alzheimer's disease. Periodontal disease, the breakdown of the connective tissues around
the teeth, is one of the most prevalent diseases on earth, affecting 47% of adults and 70% of adults over the age
of 65. The periodontal complex is a unique joint composed of two hard tissues, cementum and alveolar bone,
and an intervening and unmineralized periodontal ligament (PDL). Periodontal disease leads to destruction of
periodontal tissues and tooth loss if left untreated. Therapeutic approaches to regenerate or repair periodontal
tissues are unpredictable at present, in part because of gaps in knowledge regarding molecules guiding dental
and periodontal development. Our goal is to more successfully promote periodontal tissue repair, regeneration,
and return to function. Factors directing cementum and alveolar bone mineralization are key for proper
periodontal development and function, and likely play important roles in tissue repair. Bone sialoprotein (gene:
Ibsp; protein: BSP) is an extracellular matrix protein highly expressed during cementum and alveolar bone
formation. BSP has several putative biological roles based on its highly conserved functional domains involved
in collagen binding (hydrophobic N-terminal domain), hydroxyapatite nucleation (polyglutamic acid sequences),
and RGD-integrin cell signaling (C-terminal motif). BSP was demonstrated to be important in skeletal
development, as genetic ablation in Ibsp knockout (Ibsp-/-) mice resulted in a skeletal phenotype marked by mildly
delayed long bone mineralization and reduced trabecular bone remodeling. However, ablation of BSP causes
even more dramatic effects in dentoalveolar tissues, where Ibsp-/- mice exhibited lack of cementum, severely
hypomineralized alveolar bone, disrupted dental attachment, periodontal breakdown, and tooth loss. We
hypothesize that BSP directs osteoblast function and mineralization activities and plays an important role in
periodontal and alveolar bone repair. We will test this hypothesis in the following three aims: Aim 1: Define the
binding location of BSP on type I collagen to define spatial mechanisms by which BSP may contribute to ECM
mineralization. Aim 2: Elucidate the mechanistic roles of the RGD integrin-binding domain and the collagen-
binding domain using newly generated cementoblast cell lines and mutant mice with a knock-in mutation
inactivating the RGD motif. Aim 3: Investigate the efficacy of BSP to enhance alveolar bone healing using
exogenous native rat BSP (nBSP) to investigate its use as a therapeutic in promoting alveolar bone repair.
Importantly, insights gained will aid not only in regeneration of alveolar bone surrounding teeth or necessary for
dental implant placement, but will also be potential...

## Key facts

- **NIH application ID:** 10235469
- **Project number:** 1F30DE030358-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Michael B. Chavez
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,436
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235469

## Citation

> US National Institutes of Health, RePORTER application 10235469, Functional domains of bone sialoprotein in dentoalveolar development and healing (1F30DE030358-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10235469. Licensed CC0.

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