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神经传递、血管生成和骨生成活性在衰老加速敏感 8 号小鼠模型的老化颞下颌关节中发生改变。

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

机构信息

Department of Anatomy, Tokyo Medical University, Tokyo, Japan.

Visiting Professor, Department of Anatomy, Tokyo Medical University, Tokyo, Japan.

出版信息

J Oral Maxillofac Surg. 2024 Jan;82(1):19-35. doi: 10.1016/j.joms.2023.09.012. Epub 2023 Sep 20.

DOI:10.1016/j.joms.2023.09.012
PMID:37832598
Abstract

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.

摘要

背景

神经递质、血管生成和成骨途径的改变可能在颞下颌关节 (TMJ) 的年龄相关变化中起关键作用,但目前对此了解甚少。

目的

本研究旨在测量衰老加速敏感 8 号 (SAMP8) 小鼠中的基因和蛋白质谱之间的相关性。

研究设计

研究人员设计并使用了 3 组 2 种小鼠模型:1) 24 周龄的早期衰老 SAMP8 和 12 周和 24 周龄的对照 SAMR1(每个阶段 n = 12)。

预测因子/暴露/自变量:使用 3 种小鼠模型研究了自变量:早期衰老小鼠模型和对照小鼠模型(12 和 24 周)。

主要结果变量

主要结果变量是 CGRP、VEGF-A、CD31、LYVE-1、骨钙素、骨桥蛋白、I 型和 II 型胶原和 MMP-2。次要结果变量是组织学特征。

协变量

不适用。

分析

通过定量实时聚合酶链反应和斑点印迹分析分别鉴定了神经递质、血管生成和成骨的基因和蛋白质表达谱。通过原位杂交和免疫组织化学验证了这些事件的细胞定位。对每个结果变量进行了双变量统计。设定统计学意义为 P 值 < 0.05。

结果

24 周龄 SAMP8 小鼠(SAMP8,3.3 ± 0.39 对 SAMR1,0.001 ± 0.0001)的骨髁(BMC)中 CGRP mRNA 的表达较高(24 周)(P < 0.001)。CGRP(MF,SAMP8,28.67 ± 1.60 对 SAMR 1,6.36 ± 1.10;CMC,27.5 ± 2.12 对 9.00 ± 1.21;BMC,31.31 ± 2.81 对 7.85 ± 1.14)和 VEGF-A(MF,34.43 ± 2.45 对 14.01 ± 1.28;MD,32.69 ± 1.86 对 8.00 ± 0.91;CMC,36.60 ± 2.05 对 14.19 ± 1.25 BMC 36.49 对 12.59 ± 1.41)抗体在 24 周 TMJ 中含量较高(P < 0.01)。

结论和相关性

神经递质、血管生成和成骨途径与 SAMP8 小鼠模型中的 TMJ 衰老有关。未来,SAMP8 小鼠模型可能被证明是一种强大的模型,可用于鉴定与 TMJ 衰老相关的分子和生化事件的饲料、咬合变化和牙齿缺失的影响。

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