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)主要由增龄或咬合缺失等咬合异常引起。然而，TMJ-OA早期阶段的潜在机制及其进展仍有待充分阐明。骨性关节炎的一个主要问题是基质合成率低，软骨细胞未能超过基质降解的速率。印度刺猬(India Hedgehog，IHH)是胚胎下颌突生长和盘原基形成所必需的，也是完成出生后TMJ生长和组织所必需的。在本研究中，II型胶原和聚集素在出生后的IHH缺陷性髁状突中的表达减少，这是骨性关节炎病变的标志。本研究的目的是确定IHH在加速衰老小鼠TMJ-OA的发生发展中的作用。方法：使用两个4个月的…更老的品系：衰老加速倾向(SAMP8)小鼠和衰老加速抵抗(SAMR1)小鼠作为对照，每个品系包括40只雄性。每个菌株分为两组：(1)研磨组(MG：上下磨牙和切牙的冠被研磨至咬合消失，软面团饮食4~8周)；(2)非研磨组(NG：不磨牙或门牙研磨，硬质颗粒饮食4~8周)。结果：与正常对照组相比，MG组和MG组大鼠在4~8周的时间里，髁突软骨厚度和II型胶原(Col II)、聚集素(Aggrecan)和IHH的基因表达均明显减少，基质金属蛋白酶(MMP13)和凝血酶敏感蛋白1基序的金属蛋白酶(ADAMTS5)的基因表达逐渐增强。与SAMR1组相比，SAMP8组Col II、Aggrecan和IHH基因表达在4~8周明显降低，而ADAMTS5和MMP13基因表达在4~8周较SAMR1组显著增加。结论：咬合缺失影响下颌骨髁状突细胞外基质重塑，Hedgehog信号影响细胞外基质重塑，SAMP8组细胞外基质降解提示TMJ-OA向更严重的方向发展。较少

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