瞬时受体电位香草素受体4型通道蛋白在创伤性颞下颌关节异位骨化发生中的作用

doi:10.3969/j.issn.1674-8115.2022.12.001

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (12): 1649-1655.doi: 10.3969/j.issn.1674-8115.2022.12.001

• 论著 · 基础研究 •

瞬时受体电位香草素受体4型通道蛋白在创伤性颞下颌关节异位骨化发生中的作用

朱悦(), 顾佳颖(), 代杰文()

上海交通大学医学院附属第九人民医院口腔颅颌面科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海? 200011

收稿日期:2022-07-03 接受日期:2022-11-18 出版日期:2022-12-28 发布日期:2022-12-28
通讯作者: 代杰文 E-mail:zyyy99@sjtu.edu.cn;gujiaying_jenning@126.com;daijiewen@163.com
作者简介:朱悦(1999—)，女，本科生；电子信箱：zyyy99@sjtu.edu.cn
顾佳颖(1999—)，女，本科生；电子信箱：gujiaying_jenning@126.com。*第一联系人：朱悦和顾佳颖为共同第一作者。
基金资助:
国家自然科学基金(82071097);上海市浦江人才计划(2020PJD026)

Effect of transient receptor potential vanilloid 4 on traumatic heterotopic ossification around temporomandibular joint

ZHU Yue(), GU Jiaying(), DAI Jiewen()

Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth Peoples' Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China

Received:2022-07-03 Accepted:2022-11-18 Online:2022-12-28 Published:2022-12-28
Contact: DAI Jiewen E-mail:zyyy99@sjtu.edu.cn;gujiaying_jenning@126.com;daijiewen@163.com
Supported by:
National Natural Science Foundation of China(82071097);Shanghai Pujiang Program(2020PJD026)

摘要/Abstract

摘要：

目的·探索瞬时受体电位香草素受体4型通道蛋白（transient receptor potential vanilloid 4，TRPV4）在创伤性颞下颌关节异位骨化（traumatic heterotopic ossification around temporomandibular joint，THO-TMJ）发生中的作用。方法·将18只8周龄雄性小鼠按单纯随机抽样方法分成2组，均行一侧髁突的一半髁突软骨切除术，建立THO-TMJ小鼠模型。实验组9只小鼠术后以灌胃方式给予TRPV4阻断剂［14 mg/（kg·d）］，对照组9只小鼠给予等量生理盐水。选取术后14、30和90 d三阶段头颅样本，利用苏木精-伊红（H-E）染色、Micro CT扫描检查颞下颌关节区异位骨化的形成情况，对影像学资料进行三维重建，获取髁突的体积和表面积数据，计算异位形成的骨组织形态学指数（morphometric index，MI），并比较2组的异位骨化情况。结果·组织学染色结果显示，2组小鼠受损的髁突周围均发生活跃的软骨内成骨导致的异位骨化。Micro CT影像显示，实验组和对照组术后的TMJ区域先表现为髁突周围的组织密度逐渐升高，随后异位骨组织逐渐向髁突外增生，部分连接于关节窝，关节间隙内可见散在的骨性赘生物，但该TMJ骨性融合趋势在对照组中较明显。实验组的 MI（0.15±0.01）显著小于对照组（0.18±0.03），差异有统计学意义（P<0.05）。结论·阻断TRPV4功能有助于延缓THO-TMJ的形成和发展。

关键词: 颞下颌关节, 创伤性异位骨化, TRPV4

Abstract:

Objective ·To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) on traumatic heterotopic ossification around temporomandibular joint (THO-TMJ). Methods ·Eighteen eight-week-old male mice were divided into two groups by simple random sampling. Half right condylar cartilage was removed in every mouse. Nine mice in experimental group was administered TRPV4 blocker [14 mg/(kg·d)] via oral gavage. The same amount of saline was given to nine mice in control group. The skull samples were collected at 14, 30 and 90 d after surgery. The heterotopic ossification was evaluated by H-E staining and Micro CT scan. Three-dimensional reconstruction of the skulls was performed to measure the volume and surface area of condyles. Morphometric index (MI) was applied to indicate the degree of heterotopic ossification in both groups. Results ·H-E staining results showed that active endochondral ossification occurred around the injured condyles in both groups. Micro CT images showed that the tissue density around the condyles in both groups gradually increased in the TMJ area after operation, and then the ectopic bone tissues gradually proliferated outside the condyle, partially connecting to the joint fossa. Scattered osteophytes were seen in the joint space. The trend of TMJ bone fusion was more obvious in the control group. The morphological index of the experimental group (MI=0.15±0.01) was lower than that of the control group (MI=0.18±0.03, P<0.05). Conclusion ·Blocking TRPV4 function can help reduce the formation and progression of THO-TMJ.

Key words: temporomandibular joint, traumatic heterotopic ossification, TRPV4

中图分类号:

R782.6

朱悦, 顾佳颖, 代杰文. 瞬时受体电位香草素受体4型通道蛋白在创伤性颞下颌关节异位骨化发生中的作用[J]. 上海交通大学学报（医学版）, 2022, 42(12): 1649-1655.

ZHU Yue, GU Jiaying, DAI Jiewen. Effect of transient receptor potential vanilloid 4 on traumatic heterotopic ossification around temporomandibular joint[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(12): 1649-1655.

图/表 3

图1 建模后3个不同阶段THO-TMJ小鼠模型的颅骨Micro CT扫描冠状位图像Note： A/B.14 d after operation; C/D. 30 d after operation; E/F. 90 d after operation. Frames indicate condyle and heterotopic ossification tissue on the surgical side. Circles indicate normal condyle.

Fig 1 Micro CT examination images of the skull of THO-TMJ mouse model in three stages after surgery

图2 建模后3个不同阶段THO-TMJ小鼠模型的头颅Micro CT三维模型Note： A: Normal mouse. B. THO-TMJ mouse in the experimental group. C.THO-TMJ mouse in the control group. The yellow part indicates condyle. The red part indicates mandible. The green part indicates skull except mandible.

Fig 2 Three dimension models of the mandible and skull of THO-TMJ mouse model in three stages after surgery

图3 建模后3个不同阶段THO-TMJ小鼠模型的手术侧髁突及周围异位骨化组织H-E染色Note： A/C. Condylar structure of THO-TMJ models 14 d after operation (×50). B/D. Endochondral ossification was observed around the condyles of THO-TMJ models 14 d after operation (×100). E/G. Condylar structure of THO-TMJ models 30 d after operation (×50). F/H.Compact trabecular bone structure around the condyles of THO-TMJ models 30 d after operation (×100). I/K.Condylar structure of THO-TMJ models 90 d after surgery (×50). J/L. The trabecular bone structure around the condyles of THO-TMJ models became loose 90 d after operation (×100). HO—heterotopic ossification tissue; CO—original condyle.

Fig 3 H-E staining images of the condyles in the operative sides in THO-TMJ mouse models in three stages after surgery

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瞬时受体电位香草素受体4型通道蛋白在创伤性颞下颌关节异位骨化发生中的作用

Effect of transient receptor potential vanilloid 4 on traumatic heterotopic ossification around temporomandibular joint

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