Molecular change in condylar cartilage and subchondral bone accompanying aging and temporomandibular joint osteoarthritis

目的：颞下颌关节（TMJ）骨关节炎（OA）主要由年龄增长或咬合异常（如咬合缺失）引起。然而，TMJ-OA的早期阶段及其进展的机制仍有待充分阐明。OA的一个主要问题是基质合成速率低，软骨细胞不能超过基质降解速率。Indian hedgehog（Ihh）基因的表达对胚胎下颌髁突的生长和盘原基的形成至关重要，也是出生后TMJ生长和组织完成所必需的。在这项研究中，在出生后Ihh缺陷的髁突中，观察到髁突软骨的主要细胞外基质（ECM）成分II型胶原和聚集蛋白聚糖的表达减少，这是OA病变的指示。本研究的目的是确定Ihh在衰老加速小鼠TMJ-OA的发展中的作用，并伴随衰老和咬合丧失。 ...更多信息 - 老品系：加速衰老易感（SAMP 8）小鼠和加速衰老抵抗（SAMR 1）小鼠作为对照，每种品系包括40只雄性。将每个品系分为两组：（1）研磨组（MG：将上、下双侧磨牙和切牙的牙冠研磨至咬合丧失，并进行软面团饮食4-8周）;和（2）非研磨组（NG：不进行磨牙或切牙研磨，并进行硬颗粒饮食4-8周）。通过组织学和真实的时间聚合酶链反应的基因表达评估下颌髁突。在MG中，两种菌株均显示髁突软骨厚度和II型胶原（Col II）、聚集蛋白聚糖和Ihh的基因表达减少，基质金属蛋白酶（MMP）-13和1型血小板反应蛋白基序金属蛋白酶（ADAMTS 5）的基因表达逐渐增加，与NG相比，8周。虽然在4-8周内，与SAMR 1 MG相比，在SAMP 8 MG中观察到Col II、聚集蛋白聚糖和Ihh的基因表达显著降低，但在4 - 8周内，与SAMR 1相比，ADAMTS 5和MMP 13的基因表达显示出显著增加。结果表明咬合丧失影响细胞外基质重塑，导致下颌骨髁状突退化，hedgehog信号影响细胞外基质的重塑，SAMP 8细胞外基质的降解表明TMJ-OA向更严重的方向发展。少

Objectives : Temporomandibular joint (TMJ) osteoarthritis (OA) is mainly caused by aging or occlusal abnormalities such as loss of occlusion. However, the mechanism underlying the early stages of TMJ-OA and its progression remain to be fully clarified. One major problem in OA is the low rate of matrix synthesis and failure of chondrocytes to exceed the rate of matrix degradation. Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation, and its expression is also required for completion of post-natal TMJ growth and organization. In this study, a decrease was observed in expression of collagen II and Aggrecan, the main extra-cellular-matrix (ECM) components of condylar cartilage, in post-natal Ihh-deficient condyles, which is indicative of OA lesions. The purpose of this study was to determine the role of Ihh in the development of TMJ-OA accompanying aging and loss of occlusion in Senescence Accelerated Mouse.Methods : We used two 4-month … More -old strains : senescence-accelerated prone (SAMP8) mice and senescence-accelerated resistant (SAMR1) mice as a control, each strain comprising 40 males. Each strain was divided into two groups : (1) a milling group (MG : crowns of upper and lower bilateral molars and incisors milled to loss of occlusion and soft dough diet for 4-8 weeks) ; and (2) a non-milling group (NG : no molar or incisor milling and hard pellet diet for 4-8 weeks). The mandibular condyle was evaluated by histology and gene expression by real time polymerase chain reaction.Results : In the MG, both strains showed a reduction in thickness of the condylar cartilage and gene expression of type II collagen (Col II), Aggrecan and Ihh, and a gradual increase in gene expression of matrix metalloproteinase (MMP)-13 and metalloproteinase with thrombospondin type 1 motif-5 (ADAMTS5) over 4-8 weeks compared to in the NG. Although a significant reduction was observed in gene expression of Col II, Aggrecan and Ihh in the SAMP8 MG compared to in the SAMR1 MG over 4-8 weeks, gene expression of ADAMTS5 and MMP13 showed a significant increase compared to in SAMR1 over 4-8 weeks.Conclusion : The results suggest that loss of occlusion affects extracellular matrix remodeling, leading to degradation of the mandibular condyle, and that hedgehog signaling affects extracellular matrix remodeling.The observed degradation of extracellular matrix in SAMP8 indicated development toward more serious TMJ-OA. Less