Mertk-driven regeneration of alveolar bone

ABSTRACT Partial or complete edentulism results in a loss of oral function and esthetic concerns, which diminishes a patient’s quality-of-life. Furthermore, regeneration of tissue lost after extraction is not predictable, partially due to the complexity of the repair/regenerative process. In order to be successful, the oral tissues must navigate three components of the regenerative process: 1) wound healing, 2) resolution of endogenous inflammation and 3) promoting growth and differentiation of the native bone tissue. The primary hypothesis of this proposal is that the receptor tyrosine kinase Mertk regulates early bone formation and this can be used as a therapeutic target for alveolar bone regeneration. We have previously observed enhanced alveolar bone fill in models of pharmacological inhibition and genetic knockout of Mertk, and this project will examine the specific mechanisms through which each modality modulates alveolar bone healing. Specific Aim 1 will determine the effects of Mertk signaling on resident alveolar bone stem cells that contribute to extraction socket healing. Specific Aim 2 will examine deletion of Mertk on recruitment and phenotype of immune cells in the extraction socket underpinning alveolar bone regeneration.