Neurotransmission, Vasculogenesis, and Osteogenesis Activities are Altered in the Aging Temporomandibular Joint of the Senescence-Accelerated Prone 8 Mouse Model

Abstract

BackgroundAlterations in neurotransmission, vasculogenesis, and osteogenesis pathways that may play pivotal roles in age-related changes in the temporomandibular joint (TMJ) are poorly understood. PurposeThis study aimed to measure the associations between gene and protein profiles in senescence-accelerated prone 8 (SAMP8) mice. Study designThe investigators designed and utilized three groups of two mouse models: 1) early aging SAMP8 at 24 weeks of age and control SAMR1 at 12 and 24 wks (each stage n=12). Predictor/exposure/independent variableThe independent variable was investigated using 3 mouse models: an early aging mouse model and a control mouse model (12 wks and 24 wks). Main outcome variable(s)The primary outcome variables were CGRP, VEGF-A, CD31, LYVE-1, osteocalcin, osteopontin, type I and II collagen, and MMP-2. The secondary outcome variables were histological characteristics. CovariatesNot applicable AnalysesThe gene and protein expression profiles of neurotransmitters, vasculogenesis, and osteogenesis were identified by quantitative real-time polymerase chain reaction and dot blot analysis, respectively. The cellular localization of these events was verified by in situ hybridization and immunohistochemistry. Bivariate statistics were computed for each of the outcome variables. Statistical significance was set to a P value < 0.05. ResultsThe expression of CGRP mRNA in the bony mandibular condyle (BMC) of SAMP8 mice (SAMP8, 3.3 ±0.39 vs. SAMR1, 0.001±0.0001) was high at 24 weeks of age (24 wks) (p<0.001). Higher numbers of cells positive for CGRP (MF, 1.97±0.13 vs. 0.35±0.05; CMC, 1.86±0.15 vs. 0.62±0.08; BMC, 1.32±0.10 vs. 0.28±0.06;) and VEGF-A (MF, 2.95±0.22 vs. 0.85±0.06; MC, 11.29±0.37 vs. 9.78 ±0.35; CMC, 12.4±0.53 vs. 1.41±1.25; BMC 1.97±0.15 vs. 0.63±0.06) antibodies were found in the TMJ (p<0.01). Conclusions and relevanceThe neurotransmitter, vasculogenesis, and osteogenesis pathways are associated with TMJ aging in the SAMP8 mouse model. In the future, the SAMP8 mouse model may prove to be a robust model for identifying molecular and biochemical events underlying the effects of feeding, occlusal changes, and tooth loss in the aging TMJ.