中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (26): 5673-5679.doi: 10.12307/2025.741

• 组织构建综述 tissue construction review • 上一篇    下一篇

Notch信号通路调控髁突软骨发育及颞下颌关节炎症的作用机制

安兴启，李文晋   

  1. 山西医科大学口腔医学院，山西省太原市  030000

  • 收稿日期:2024-08-28 接受日期:2024-11-02 出版日期:2025-09-18 发布日期:2025-02-28
  • 通讯作者: 李文晋，博士，主任医师，山西医科大学口腔医学院，山西省太原市 030000
  • 作者简介:安兴启，男，1997年生，山西省忻州市人，汉族，2025年山西医科大学毕业，硕士，医师，主要从事颌面部骨生长发育的影响因素研究。
  • 基金资助:
    山西省留学人员科技活动择优资助项目(20240048)，课题名称：Shh信号通路调控miRNA-1小鼠下颌生长发育的实验研究，项目负责人：李文晋；山西省自然科学研究面上项目(202303021211214)，课题名称：miR-1通过Hedgehog信号通路调控小鼠下颌骨生长发育的实验研究，项目负责人：李文晋

Mechanism of Notch signaling pathway regulating condylar cartilage development and temporomandibular joint inflammation

An Xingqi, Li Wenjin   

  1. School of Stomatology, Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
  • Received:2024-08-28 Accepted:2024-11-02 Online:2025-09-18 Published:2025-02-28
  • Contact: Li Wenjin, MD, Chief physician, School of Stomatology, Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
  • About author:An Xingqi, MS, Physician, School of Stomatology, Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
  • Supported by:
    Shanxi Province Overseas Educated Scholars Science and Technology Activities Merit-Supported Project, No. 20240048 (to LWJ); Shanxi Province Natural Science Research General Project, No. 202303021211214 (to LWJ)

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摘要：


文题释义：
Notch信号通路：是一种与骨骼生长发育密切相关的配体依赖性通路，Notch相关的受体、配体及信号通路中下游因子的表达能够影响髁突软骨细胞的增殖与分化。 
髁突软骨：是颌面部最重要的解剖结构之一，参与颞下颌关节的正常发育及行使功能，当调控髁突软骨生长发育的因子异常表达时，髁突软骨会发生变性，造成颞下颌关节炎症。

背景：髁突是颌面部最重要的解剖结构，人体行使咀嚼、发音等功能时髁突有着极为重要的作用，其发育过程同一般骨组织差异较大，髁突软骨的异常发育会导致各类不同程度的颞下颌关节疾病，影响患者的生活质量。Notch信号通路的异常传导不仅影响髁突软骨发育及形成过程，还会导致颞下颌关节紊乱等一系列相关疾病。然而，目前Notch信号通路与髁突软骨生长发育及颞下颌关节疾病之间的作用机制尚未完全阐明，
目的：深入研究Notch与髁突软骨生长发育之间的作用机制，并且围绕Notch作为颞下颌关节炎的治疗靶点这一核心展开相关机制的讨论。
方法：使用文献资料法，以中英文核心关键词在中国知网和PubMed数据库进行检索、查找，通过对比分析法对所查找的文献进行比较，排除内容相近的文献，比较筛选后文献之间的差异，选取所需要的内容，为文章的撰写提供理论依据；通过将筛查后的文献进一步研究分析，明确各因子之间的作用机制，为行文提供清晰的思路。共检索出1 848篇相关文献，最终纳入53篇文献进行综述。
结果与结论：①髁突软骨的生长发育方式较其他骨更为复杂，经历了软骨内成骨过程；髁突软骨细胞分化易受到多种因素影响，进而最终影响成软骨及成骨；②Notch信号通路近年来广受关注，它在髁突生长发育过程中也起到非常重要的作用；③Notch信号通路主要包括4部分：4种Notch受体(Notch 1-4)，5种Notch配体(JAG 1/2、DLL 1/3/4)，细胞内转录因子(CSL结合蛋白)，多个靶基因Hes、Hey等；其主要作用途径分为2种：典型途径与非典型途径；④Notch信号通路发挥调控作用时会受到体内γ分泌酶抑制剂或甲状旁腺激素相关蛋白等因素的干扰，常见的受体及配体等因子表达异常，进而影响髁突软骨生长发育；⑤除体内各种因素之外，异常的咀嚼应力及颞下颌关节受到过大的负荷也会影响Notch信号通路的正常传导，造成髁突软骨的异常发育；⑥Notch信号通路也会影响颞下颌关节炎，异常的信号传导能够影响颞下颌关节炎的发病进程。
https://orcid.org/0009-0009-3695-2162(安兴启)；https://orcid.org/0000-0002-4555-5857(李文晋)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: Notch信号通路, 髁突软骨, 髁突软骨细胞, 颞下颌关节, 颞下颌关节炎症, 颅颌面部骨骼, 通路机制, 工程化组织构建

Abstract: BACKGROUND: The condyle is the most important anatomical structure of the maxillofacial region, and it plays an important role in mastication and articulation of the human body, and its developmental process is quite different from that of the general bone tissues. Abnormal development of the condylar cartilage can lead to various temporomandibular joint disorders to varying degrees, which affects the patient’s quality of life. Abnormal conduction of Notch signaling not only influences the developmental process of the condylar cartilage, but also leads to a series of related diseases such as temporomandibular joint disorders. Aberrant Notch signaling not only affects condylar cartilage development and formation, but also leads to a series of related diseases such as temporomandibular joint disorders. However, the role of Notch signaling pathway in condylar cartilage development and temporomandibular joint disorders has not been fully elucidated. 
OBJECTIVE: To deeply investigate the mechanism of Notch and condylar cartilage growth and development, and discuss the core of Notch as a therapeutic target for temporomandibular joint arthritis.
METHODS: We retrieved, searched and screened relevant literature in CNKI and PubMed with the keywords “Notch signaling pathway, condylar chondrocyte, condylar cartilage, temporomandibular arthritis” in Chinese and English respectively to provide a theoretical basis for the full text. Using comparative analysis method, we compared the retrieved literature, excluded the literature with similar content, compared the differences between the screened literature, and selected the content needed for this article, providing the theoretical basis for the writing of the article. By further studying and analyzing the screened literature, the mechanism of action between the factors was clarified to provide a clear idea for the article. A total of 1 848 relevant papers were retrieved and 53 papers were finally included for review.
RESULTS AND CONCLUSION: (1) The condylar cartilage grows and develops in a more complex manner than other bones, and it undergoes an endochondral osteogenesis. Condylar chondrocyte differentiation is susceptible to a variety of factors, which ultimately affects the formation of cartilage and osteoblasts. (2) The Notch signaling pathway has attracted much attention in recent years, and plays a very important role in condylar growth and development. (3) The Notch signaling pathway consists of four components: four Notch receptors (Notch 1-4), five Notch ligands (JAG 1/2 and DLL 1/3/4), intracellular transcription factors (CSL-binding proteins), and multiple target genes such as Hes and Hey. The Notch signaling pathway is divided into two main pathways: typical pathway and atypical pathway. (4) The Notch signaling pathway is interfered with by factors such as γ-secretase inhibitors or parathyroid hormone-related proteins in vivo, and common factors such as receptors and ligands are expressed abnormally, thus affecting condylar cartilage growth and development. (5) In addition to the various factors in the body, abnormal masticatory stress and excessive loading of the temporomandibular joint can also affect the normal transmission of the Notch signaling pathway, resulting in the abnormal development of the condylar cartilage. (6) The Notch signaling pathway also affects temporomandibular joint arthritis, and the abnormal signaling can affect the pathogenesis of temporomandibular joint arthritis.

Key words: Notch signaling pathway, condylar cartilage, condylar chondrocytes, temporomandibular joint, temporomandibular joint inflammation, craniomaxillofacial skeleton, pathway mechanism, engineered tissue construction

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