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

Background: Alterations in neurotransmission, vasculogenesis, and osteogenesis pathways that may play pivotal roles in age-related changes in the temporomandibular joint (TMJ) are poorly understood. Purpose: This study aimed to measure the associations between gene and protein profiles in senescence-accelerated prone 8 (SAMP8) mice. Study Design: The investigators designed and used 3 groups of 2 mouse models: 1) early aging SAMP8 at 24 weeks of age and control SAMR1 at 12 and 24 weeks (each stage n = 12). Predictor/Exposure/Independent Variable: The independent variable was investigated using 3 mouse models: an early aging mouse model and a control mouse model (12 and 24 weeks). 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. Covariates: Not applicable. Analyses: The 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 < .05. Results: The 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 weeks) (P < .001). Higher numbers of cells positive percentage for CGRP (MF, SAMP8, 28.67 1.60 vs SAMR 1, 6.36 1.10; CMC, 27.5 +/- 2.12 vs 9.00 +/- 1.21; BMC, 31.31 2.81 vs 7.85 1.14) and VEGF-A (MF, 34.43 2.45 vs 14.01 1.28; MD, 32.69 +/- 1.86 vs 8.00 +/- 0.91; CMC, 36.60 +/- 2.05 vs 14.19 +/- 1.25 BMC 36.49 vs 12.59 +/- 1.41) antibodies were found in the 24 weeks TMJ (P < .01). Conclusions and Relevance: The 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. (c) 2023 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 82:19-35, 2024