Asporin stably expressed in the surface layer of mandibular condylar cartilage and augmented in the deeper layer with age.
Asporin stably expressed in the surface layer of mandibular condylar cartilage and augmented in the deeper layer with age.
复制标题
Asporin稳定地在下颌骨软骨的表面层中表达，并随着年龄的增长而在更深的层中增强。
DOI：
10.1016/j.bonr.2017.07.002
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发表时间：
2017-12
期刊：
影响因子：
2.5
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
作者：
Miyamoto Y;Kanzaki H;Wada S;Tsuruoka S;Itohiya K;Kumagai K;Hamada Y;Nakamura Y
下颌骨髁状突软骨具有关节软骨和生长中心的双重作用。在众多的生长因子中，转化生长因子-β参与了包括肾小管细胞癌在内的关节软骨的生长。最近发现了转化生长因子-β的诱饵阿司匹林，它能阻断转化生长因子-β信号转导。Asporin在包括骨关节炎关节软骨在内的多种组织中都有表达，但尚未见Asporin在MCC中表达的报道。在本研究中，我们研究了Asporin在MCC中的时空表达。首次利用激光捕获显微解剖标本，用基因芯片技术比较了5周龄ICR小鼠胫骨MCC和骨骺软骨的基因表达谱。在1、3、10和20周龄时，通过实时荧光定量RT-PCR和免疫组织化学染色进一步证实基因表达的差异。用免疫组织化学方法检测转化生长因子-β及其信号分子磷酸化Smad2/3(p-Smad2/3)的表达。基因芯片分析表明Asporin在MCC中高表达。实时荧光定量RT-PCR分析证实，在任何时间点，MCC纤维层的Asporin表达均稳定高于骨骺软骨。免疫组织化学染色也观察到这一点。MCC深层随年龄增长Asporin表达增强。而转化生长因子-β在该层中稳定地高表达。MCC纤维层中p-Smad2/3的表达较弱，而增殖层中p-Smad2/3的表达在早期呈强阳性。随着MCC深层Asporin表达的增加，p-Smad-2/3的表达强度随增龄而减弱。综上所述，我们发现Asporin在MCC的纤维层稳定表达，这使得同时管理关节软骨和生长中心成为可能。Asporin基因和蛋白在下颌骨平台软骨中的表达高于胫骨平台软骨。随着年龄的增长，下颌骨髁突软骨中Asporin的含量逐渐增加。转化生长因子-β信号通路被Asporin增强抑制，转化生长因子-β在下颌骨软骨中的表达减少。
Mandibular condylar cartilage (MCC) exhibits dual roles both articular cartilage and growth center. Of many growth factors, TGF-β has been implicated in the growth of articular cartilage including MCC. Recently, Asporin, decoy to TGF-β, was discovered and it blocks TGF-β signaling. Asporin is expressed in a variety of tissues including osteoarthritic articular cartilage, though there was no report of Asporin expression in MCC. In the present study, we investigated the temporal and spatial expression of Asporin in MCC. Gene expression profile of MCC and epiphyseal cartilage in tibia of 5 weeks old ICR mice were firstly compared with microarray analysis using the laser capture microdissected samples. Variance of gene expression was further confirmed by real-time RT-PCR and immunohistochemical staining at 1,3,10, and 20 weeks old. TGF-β and its signaling molecule, phosphorylated Smad-2/3 (p-Smad2/3), were also examined by immunohistochemical staining. Microarray analysis revealed that Asporin was highly expressed in MCC. Real-time RT-PCR analysis confirmed that the fibrous layer of MCC exhibited stable higher Asporin expression at any time points as compared to epiphyseal cartilage. This was also observed in immunohistochemical staining. Deeper layer in MCC augmented Asporin expression with age. Whereas, TGF-β was stably highly observed in the layer. The fibrous layer of MCC exhibited weak staining of p-Smad2/3, though the proliferating layer of MCC was strongly stained as compared to epiphyseal cartilage of tibia at early time point. Consistent with the increase of Asporin expression in the deeper layer of MCC, the intensity of p-Smad-2/3 staining was decreased with age. In conclusion, we discovered that Asporin was stably expressed at the fibrous layer of MCC, which makes it possible to manage both articular cartilage and growth center at the same time. Asporin gene and protein were highly expressed in mandibular condylar cartilage as compared to tibial epiphyseal cartilage. Asporin in mandibular condylar cartilage was augmented with age. TGF-β signaling is suppressed by augmented Asporin and decreased TGF-β production in mandibular condylar cartilage.