Int J Stomatol

Int J Stomatol ›› 2021, Vol. 48 ›› Issue (5): 556-562.doi: 10.7518/gjkq.2021099

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The role of follistatin in oral and maxillofacial development and its therapeutic application prospect

Liu Jiacheng1(),Meng Zhaosong2,Li Hongjie1,Sui Lei3()   

  1. 1. Dept. of Pathology, School & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
    2. Dept. of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
    3. Dept. of Prosthodontics, School & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
  • Received:2021-02-21 Revised:2021-06-06 Online:2021-09-01 Published:2021-09-10
  • Contact: Lei Sui E-mail:928299023@qq.com;suilei@tmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81700927)

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Abstract:

Follistatin (FST) is a single-chain glycoprotein synthesized and secreted by pituitary, liver, bone, and other tissues. It has extensive tissue distribution and a variety of physiological and pathological functions proven to have therapeutic value in inflammation, bone injury, and muscle atrophy by in vivo and in vitro experiments. Recent studies have demonstrated that FST plays a key role in maintaining the homeostasis of oral and maxillofacial tissues. FST has potential value in the treatment of oral inflammation, bone injury, and other diseases and is particularly important for the development of soft and hard tissues, such as teeth, lip, palate, and jaw. FST expresses in oral and maxillofacial epithelium and mesenchyme, where it antagonizes the transforming growth factor-β signaling pathway through binding to activin and bone morphogenetic proteins. Therefore, it participates in the regulation of oral and maxillofacial development as well as the occurrence and development of related diseases. This paper focuses on the role, mechanism, and application prospect of FST in oral and maxillofacial development and diseases in order to lay a foundation for its further research and clinical application in the field of stomatology.

Key words: follistatin, growth and development, squamous cell cancer, inflammation, bone regeneration

CLC Number: 

  • R782

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Fig 1

The mechanism of FST in regulation of ACT and BMPs signaling pathways"

Tab 1

The distribution and functions of FST target protein signaling pathway components in oral and maxillofacial region and the mechanism of FST on them"

信号通路 信号蛋白 主要表达细胞 生理功能 FST作用机制
ACT信号
通路		 ACT[16-17,34] 牙间充质细胞、成骨细胞 参与早期骨和牙胚的形成及破骨细胞分化 FST二聚体与ACT二聚体构成复合体,使ACT与受体结合受阻
Smad2[18,29,38] 牙上皮、间充质细胞、成牙本质细胞、单核巨噬细胞 参与中胚层和下颌骨的发育,调控釉质、牙本质、破骨细胞的形成 磷酸化受阻
Smad3[18,38] 同Smad2 调控釉质、牙本质的形成和破骨细胞分化 同Smad2
通用传导
蛋白		 Smad4[19-20,30] 牙上皮、间充质细胞、成牙本质细胞 参与第一鳃弓、面突和正常牙体的发育,维持牙源性干细胞稳态 招募及入核受阻
BMP信号
通路		 BMP2[21-23,28,34] 成骨细胞、牙上皮、间充质细胞、成牙本质细胞 参与早期骨形成及腭发育、牙根发育,促进成牙本质细胞和成釉细胞分化 1分子FST、1分子BMP与1分子Ⅱ型BMP受体构成复合体,使Ⅰ型BMP受体磷酸化受阻
BMP4[16,28,39] 成骨细胞、成釉细胞、牙间充质细胞 参与早期骨形成和腭发育,调控成釉细胞分化和釉质形成,参与上皮间充质的相互作用 同BMP2
BMP7[16,24,39] 成骨细胞、前成釉细胞、前成牙本质细胞 参与早期骨形成,维持HERS正常结构 同BMP2
Smad1[21-23,36-37] 同BMP2 参与BMP2的生理过程 磷酸化受阻
Smad5[21-23,36-37] 同BMP2 参与BMP2的生理过程 同Smad1
Smad8[21-23,36-37] 同BMP2 参与BMP2的生理过程 同Smad1
Smad9[36] 成骨细胞 参与BMP2骨调控过程 同Smad1
GDF11[25,26] 胚胎期面部上皮、间充质细胞 参与唇、腭发育 FST二聚体与GDF11二聚体构成复合体,使GDF11与受体结合受阻

Fig 2

The prospect of therapeutic applications of FST"

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