正常和发育不良髋臼软骨中未折叠蛋白反应的鉴定

Q4 Medicine

中华小儿外科杂志 Pub Date : 2019-11-15 DOI:10.3760/CMA.J.ISSN.0253-3006.2019.11.016

Xiaoyan Ni, Yifeng Lin, Xinhong Pei

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引用次数: 0

摘要

目的探讨未折叠蛋白在正常和发育不良髋臼软骨中的作用。方法采用髋部保持襁褓位的方法，建立大鼠髋臼发育不良模型。采用苏木精伊红染色法观察正常和DDH模型髋臼软骨的形态特征，测量生长板宽度，包括肥厚带(HZ)和增殖带(PZ)。采用定量聚合酶链反应(qPCR)检测不同时间点软骨细胞分化标志物(Sox9、Col2a1、Acan)和肥厚标志物(Runx2、Col10a1、Mmp13) mRNA表达量。分别用qPCR和免疫组化方法检测Grp78、P50ATF6、XBP1s和磷酸化eIF2α的未折叠蛋白应答基因的表达。结果a)与对照组相比，随着DDH的进展，髋臼上侧变平。生长板中的细胞受到干扰，失去极性。生长板肥厚带(HZ)和增殖带(PZ)宽度显著缩短(P<0.05);b) Sox9、Col2a1、Acan和Runx2、Col10a1、Mmp13 mRNA表达量呈时间依赖性显著降低(P<0.05);c) Grp78 mRNA在髋臼软骨中的表达明显受到抑制(P<0.05)。与未折叠蛋白反应相关的XBP1s、P50ATF6和P - eif2 α蛋白在生长板中的表达均被显著抑制(P<0.05)。结论软骨细胞分化和软骨内成骨需要生理的未折叠蛋白反应参与，而未折叠蛋白反应在DDH模型中被抑制，干扰正常的软骨细胞成熟和软骨内成骨。因此，它可能在一定程度上参与了髋臼软骨发育不良的病理过程。关键词:髋臼;软骨;未折叠蛋白反应;髋关节发育不良;软骨细胞分化

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Identification of unfolded protein response in normal and dysplastic acetabular cartilage

Objective To explore the role of unfolded protein response in normal and dysplastic acetabular cartilages. Methods The rat model of dysplastic acetabulum was established by maintaining hips in a swaddling position.Hematoxylin & eosin staining was utilized for observing the morphological characteristics of acetabular cartilage in normal and DDH models and the width of growth plate measured, including hypertrophic zone (HZ) and proliferative zone (PZ). The mRNA expressions of chondrocyte differentiating markers (Sox9, Col2a1 & Acan) and hypertrophic markers (Runx2, Col10a1 & Mmp13) were measured by quantitative polymerase chain reaction (qPCR) at different timepoints.The expressions of unfolded protein response genes of Grp78, P50ATF6, XBP1s and phosphorylated eIF2α were detected by qPCR and immunohistochemistry respectively. Results a) As compared with control, upper side of acetabulum became flatter with the progression of DDH.Cells in growth plate were disturbed with a loss of polarity.The width of hypertrophic zone (HZ) and proliferative zone (PZ) of growth plates became significantly shortened(P<0.05); b) The mRNA expressions of Sox9, Col2a1 and Acan and Runx2, Col10a1 and Mmp13 decreased significantly in a time-dependent manner(P<0.05); c) The mRNA expressions of Grp78 were markedly inhibited in acetabular cartilages(P<0.05). The protein expressions of XBP1s, P50ATF6 and p-eIF2α involved in unfolded protein response were significantly suppressed in growth plates(P<0.05). Conclusions Chondrocyte differentiation and endochondral ossification require the participation of a physiological unfolded protein response whereas unfolded protein response is inhibited in DDH model, interfering with normal chondrocyte maturation and endochondral ossification.Thus it may be somewhat involved in the pathological process of dysplastic acetabular cartilage. Key words: Acetabulum; Cartilage; Unfolded protein response; Developmental dysplasia of the hip; Chondrocyte differentiation

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来源期刊

中华小儿外科杂志 Medicine-Pediatrics, Perinatology and Child Health

CiteScore

0.40

自引率

0.00%

发文量

8707

期刊介绍： Chinese Journal of Pediatric Surgery is an academic journal sponsored by the Chinese Medical Association. It mainly publishes original research papers, reviews and comments in this field. The journal was founded in 1980 and is included in well-known databases such as Peking University Journal (Chinese Journal of Humanities and Social Sciences) and CSCD Chinese Science Citation Database Source Journal (including extended version). It is one of the national key academic journals under the supervision of the China Association for Science and Technology. Chinese Journal of Pediatric Surgery enjoys a high reputation and influence in the academic community. The articles published in this journal have a high academic level and practical value, providing readers with a large number of practical cases and industry information, and have received widespread attention and citations from readers.