GGrantIndex
← Search

Functional Competence of a Dentoalveolar Fibrous Joint in Vertebrates

$383,563R01FY2021DENIH

University Of California, San Francisco, San Francisco CA

Investigators

Linked publications & trials

Abstract

ABSTRACT A variety of biomechanical stimuli are directed on the dentoalveolar fibrous joint (DAJ) of the masticatory complex (e.g. chewing on softer diet (SD), therapeutic loads from orthodontic interventions), and can result in local abnormal deformations and adaptive processes that can lead to aberrant function [1-7]. A systematic study of the effect of SD on the tooth-crown revealed significant age-related shifts in biological processes in the periodontal complex (R01DE022032 02/2012-01/2018). Thus, recovery of an adapting joint to its original stiffness is compromised with age, but the question remained: when the joint is exposed to prolonged aberrant loads, what is the optimal age range for the joint to recover to its baseline biomechanics should the aberrant load be substituted with physiologic loads (hard diet (HD))? What is the age range beyond which joint biomechanics are irreversible? Data from the recovery model (RM) (mice raised to various time points on SD and switched to HD), will help determine the age range for which functional competence of the joint is maintained, and help predict when clinical intervention simulated through an experimental tooth movement (ETM) model is most effective. ETM will also help in identifying the intended reversal of natural biological processes [8] at the strain-amplified sites of the PDL-entheses. Hypothesis: The functional competence of the DAJ can be identified as age-related gradients in biological expressions (?BE/?age) and joint stiffness (?S/?age). From a translational perspective, ETM is effective in an age range that demonstrates minima in ?S/?age. Proposed aims will include: Aim 1: To assess the recovery of functional competence of adapting fibrous joints with age. Functional competence of an adapted joint will be determined by its ability to resist shifts in magnitudes and frequencies of biomechanical loads without subsequent pathologic function [9]; to-date no such data exist. Functional competence will be determined from digital spatiotemporal maps of changes in periodontal ligament (PDL)-spaces, tooth-bone morphology and joint stiffness (?S/?age) with age from SD, HD, RM groups. The RM will identify an age range to optimize preservation of the fibrous joint. Aim 2: To assess the mechanobiological processes of an adapting fibrous joint with age. Spatiotemporal shifts in biological expressions (BE) (?BE/?age ? genes and matrix proteins) at the bone, cementum, and the PDL-entheses from respective age groups will be mapped. Differentially expressed genes, and mineral forming and resorbing matrix factors at PDL-entheses and the PDL at widened and narrowed regions with age for three groups (SD, HD, RM) will be correlated. AIM 3: To assess the effect of a proposed age range on experimental tooth movement resulting in long-term functional competence. Outcome physicochemical and biological measures will be the same as in Aims 1 and 2 but on ETM group [10] before, during, and after the proposed age range from the RM in Aims 1 and 2. The intended reversal of natural biological process at the strain-amplified PDL-entheses in the ETM model also will be investigated.

View original record on NIH RePORTER →