北京大学学报(医学版) ›› 2021, Vol. 53 ›› Issue (1): 34-39. doi: 10.19723/j.issn.1671-167X.2021.01.006

• 论著 • 上一篇    下一篇

软骨寡聚基质蛋白在颞下颌关节滑膜软骨瘤病中的表达

韩玮华1,罗海燕2,郭传瑸1,宁琦1,孟娟红1,Δ()   

  1. 1.北京大学口腔医学院·口腔医院,颌面外科, 国家口腔疾病临床医学研究中心 口腔数字化医疗技术和材料国家工程实验室 口腔数字医学北京市重点实验室,北京 100081
    2.北京大学口腔医学院·口腔医院,病理科 国家口腔疾病临床医学研究中心 口腔数字化医疗技术和材料国家工程实验室 口腔数字医学北京市重点实验室,北京 100081
  • 收稿日期:2020-10-12 出版日期:2021-02-18 发布日期:2021-02-07
  • 通讯作者: 孟娟红 E-mail:jhmeng@263.net

Expression of cartilage oligomeric matrix protein in the synovial chondromatosis of the temporomandibular joint

HAN Wei-hua1,LUO Hai-yan2,GUO Chuan-bin1,NING Qi1,MENG Juan-hong1,Δ()   

  1. 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
    2. Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
  • Received:2020-10-12 Online:2021-02-18 Published:2021-02-07
  • Contact: Juan-hong MENG E-mail:jhmeng@263.net

摘要:

目的: 检测软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)在颞下颌关节滑膜软骨瘤病(synovial chondromatosis of the temporomandibular joint,TMJSC)中的表达,并初步探讨其在TMJSC发病中可能的作用。方法: 选取2011年1月至2020年2月于北京大学口腔医院就诊的有完整病历资料、经手术治疗且术后病理诊断为TMJSC的患者,通过免疫组织化学实验、蛋白免疫印记法及实时荧光定量PCR,分别在蛋白、mRNA水平检测TMJSC中COMP、转化生长因子(transforming growth factor,TGF)-β3、TGF-β1、骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)等细胞因子的表达情况,并与正常滑膜组织进行比较。显微镜下观察病变的组织形态学特征、蛋白表达及分布情况,对阳性染色蛋白进行半定量分析;采用SPSS 22.0统计软件对实验结果进行分析,P<0.05表示差异有统计学意义。结果: 免疫组织化学实验结果显示,TMJSC组织中COMP阳性表达多见于滑膜组织及与滑膜邻近的软骨细胞内,与正常滑膜组织相比表达明显增多;TMJSC复发病例中COMP阳性表达评分较未复发病例更高;TGF-β3、TGF-β1及BMP-2阳性表达分布与COMP类似,表达水平较正常滑膜组织明显增高;该结论在蛋白免疫印迹法中得到进一步印证。实时荧光定量PCR检测结果显示,COMPTGF-β3TGF-β1BMP-2的表达较正常滑膜组织均有增高。结论: COMP在TMJSC中表达显著增高,并与TGF-β3、TGF-β1及BMP-2间存在协同作用,可能在该肿瘤的发病中起一定作用。

关键词: 颞下颌关节, 滑膜软骨瘤病, 软骨寡聚基质蛋白, 转化生长因子, 骨形态发生蛋白-2

Abstract:

Objective: To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC),and to discuss the possible interactions between COMP, transforming growth factor (TGF)-β3, TGF-β1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease.Methods: Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P<0.05 indicated that the difference was statistically significant.Results: Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-β3, TGF-β1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue.Conclusion: The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-β3, TGF-β1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.

Key words: Temporomandibular joint, Synovial chondromatosis, Cartilage oligomeric matrix protein, Transforming growth factor, Bone morphogenetic protein-2

中图分类号: 

  • R782.6

表1

mRNA 引物序列"

mRNA template Primer sequence
COMP Forward: 5'-CAGATGGAGCAAACGTATTGG-3'
Reverse: 5'-GAAGACTTCACAGCCTTGAGTT-3'
TGF-β3 Forward: 5'-CTGTTGAGAAGAGAGTCCAACT-3'
Reverse: 5'-GATTTCCATCACCTCGTGAATG'-3'
TGF-β1 Forward: 5'-CTGTACATTGACTTCCGCAAG-3'
Reverse: 5'-TGTCCAGGCTCCAAATGTAG-3'
BMP-2 Forward: 5'-GACGTTGGTCAACTCTGTTAAC-3'
Reverse: 5'-GTCAAGGTACAGCATCGAGATA-3'

图1

TMJSC组织学形态(HE ×100)"

图2

正常颞下颌关节和TMJSC滑膜相关蛋白的免疫组织化学表达结果"

表2

TMJSC中相关蛋白的免疫组织化学表达"

Proteins Distribution of protein expression score, n Positive rate/%,
Median
+ ++ +++ Total
COMP 0 19 33 52 47.80
TGF-β3 0 24 28 52 40.50
BMP-2 0 42 10 52 35.35
TGF-β1 2 37 13 52 15.00

表3

TMJSC复发和未复发病例间免疫组织化学COMP半定量蛋白表达差异"

Groups Semi-quantitative protein
expression of COMP, n
Total
- + ++ +++
Recurrent TMJSC 0 0 0 4 4
Non-recurrent TMJSC 0 0 23 25 48
Normal synovium 3 0 0 0 3
Total 3 0 23 29 55

图3

TMJSC与正常滑膜中相关蛋白表达差异"

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