Funded Projects
Genetic Determinants of Alveolar Bone Homeostasis
Funded November 2021
Submitted by Keith Kirkwood
Description
Alveolar bone is a unique osseous tissue that houses teeth near the oral mucosa and its resident microbiome community. Similar to long bone, systemic endocrine factors and metabolism influence alveolar bone homeostasis. However, alveolar bone is highly dependent on the inflammatory status of adjacent gingival tissues, reflecting the immunological interaction of the gingival barrier and oral microbial commensals. Consequently, many different interactions between structural, endocrine and immune tissue components—influenced by genetics—could ultimately have catabolic effects disrupting alveolar bone homeostasis.
Host genetic variation is associated with mineral density, strength and structure of long bones. Heritable factors account for as much as 80% of the variability in long bone mineral density. Thus, it is likely that genetics exert a major influence on bone remodeling of the alveolar processes, however; the specific genetic determinants of alveolar bone homeostasis are not completely elucidated. Inflammation-mediated alveolar bone resorption (i.e. periodontitis) has been shown to be dependent on genetics.
Here, we propose to explore the heritability of alveolar bone loss natural homeostasis in a population of outbred rats (the heterogenous stock (HS) rat model). We will take advantage of an existing ongoing NIH-funded study in which HS rats are being used to explore genetic determinants of cocaine addiction (P50DA037844). HS rats were derived from 8 founder strains and have been used to fine map quantitative trait loci (QTL) for diabetes, obesity, behavioral phenotypes and osteoporosis. For the Blue-Sky Collaborative Trio, we will: 1) evaluate phenotypic variability via alveolar bone micro CT scans, and 2) evaluate variability in the rat oral microbiome and its association with alveolar bone phenotype and genetics. Our goal is to gather preliminary data for a grant submission to explore genetic determinants of alveolar bone loss.
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