# Functions of extracellular matrix proteins in dental and skeletal mineralization

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $366,795

## Abstract

PROJECT SUMMARY/ABSTRACT
The periodontal complex, including cementum, periodontal ligament (PDL), and alveolar bone, is critical for tooth
attachment and function. Periodontal diseases are among the most prevalent on earth, causing periodontal
destruction and tooth loss, and affecting health and quality of life. Periodontal regeneration is possible, however,
current therapies are unpredictable, few are truly regenerative, and many lack a biologic foundation. The path
to regeneration remains unclear, in part, because origins and differentiation of cementoblasts (cells that produce
cementum), and regulatory processes in cementogenesis, remain poorly understood. Bone sialoprotein (Ibsp
gene; BSP protein) is a multifunctional extracellular matrix (ECM) protein associated with mineralized tissues,
skeletal formation, and bone remodeling. Ibsp knockout (Ibsp-/-) mice feature absence of functional acellular
cementum, PDL detachment, defective alveolar bone and cellular cementum mineralization, and alveolar bone
resorption and tooth loss. The underlying mechanisms of BSP function remain unknown, although BSP harbors
three functional domains, including a collagen-binding domain, polyglutamic acid (polyE) motifs that promote
mineralization, and an arginine-glycine-aspartic acid (RGD) integrin-binding domain that initiates cell signaling.
We propose that BSP is a unique candidate factor for studying cementum formation and alveolar bone healing
because it is selectively expressed, essential for proper function, and operates by non-redundant mechanism(s)
distinct from other growth factors. Based on our preliminary data, our hypotheses are that cementoblasts are
BSP-expressing ectomesenchymal cells distinct from osteoblasts; BSP signals bone cells via the RGD domain
in bone remodeling and directs mineral deposition onto collagen fibrils via the collagen-binding domain; and BSP
promotes alveolar bone healing. These hypotheses will be tested by 3 specific aims: (1) To define the origin and
transcriptome of cementoblasts using conditional ablation of Ibsp from ectomesenchymal vs. epithelial cell
populations, and use endogenous yellow fluorescent protein expression in Ibsp-topaz mice to ex vivo purify
cementoblasts by fluorescence-activated cell sorting (FACS) and perform transcriptomic analysis; (2) To analyze
the mechanism by which BSP functions in bones and teeth by defining the binding site of BSP on collagen and
analyzing inactivation of BSP RGD and collagen-binding domains in cementoblasts in vitro and genetically
engineered mouse lines in vivo; and (3) To evaluate the role of BSP in alveolar bone repair using a molar socket
healing model in mice and an osteotomy healing model in human subjects to map BSP expression, and
determine healing outcomes in mice when BSP is ablated or specific functional domains have been inactivated.

## Key facts

- **NIH application ID:** 10418757
- **Project number:** 5R01DE027639-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Brian Lee Foster
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $366,795
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418757

## Citation

> US National Institutes of Health, RePORTER application 10418757, Functions of extracellular matrix proteins in dental and skeletal mineralization (5R01DE027639-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10418757. Licensed CC0.

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