TRPV4对种植体周围纤维组织形成的调控作用

doi:10.19439/j.sjos.2026.04.002

摘要/Abstract

摘要： 目的: 探讨不同条件下种植体坚硬表面瞬时受体电位香草素4（transient receptor potential vanilloid 4, TRPV4）对种植体周围成纤维组织愈合的影响,初步探索其在炎症反应和纤维化过程中的调控机制。方法: 体外实验将小鼠成纤维细胞随机分为NC组（培养在普通6孔板上）、B14组（培养在6孔板硬基质玻片上）和BH14组（培养在玻片上+TRPV4抑制剂HC-067047）,采用PCR检测各组TRPV4表达水平。体内实验选取TRPV4基因敲除小鼠[TRPV4（-/-）组,n=20]和同背景野生型小鼠[TRPV4（+/+）组,n=20],建立种植体植入模型,随机分为种植组与种植周围炎组两个亚组。术后于不同时间点观察种植体周围软组织愈合情况,通过Micro-CT扫描评估种植体周围骨结合情况,HE观察炎症浸润情况及种植体周围软组织破坏情况,Masson染色检测各组胶原纤维变化,IHF检测巨噬细胞CD68及肌成纤维细胞（α-SMA）的表达变化,PCR及ELISA检测相关炎症因子的表达水平。透射电镜下观察各组上皮结构、成纤维细胞及细胞外基质变化。结果: 术后7~30天,TRPV4(+/+)小鼠种植体周围软组织修复较慢,炎症反应持续,纤维化现象明显;TRPV4(-/-)小鼠软组织愈合较快,炎症反应明显减轻,纤维化程度较低。30天后表现渐趋一致,IHF结果显示,炎症状态下TRPV4促进巨噬细胞活化和成纤维细胞向肌成纤维细胞（α-SMA）转化,推动纤维化进程。观察TRPV4的表达与YAP/TEAD相关蛋白表达水平的相关性,结果提示TRPV4可能通过YAP/TEAD信号通路调节纤维化过程。结论: TRPV4在种植体周围软组织的愈合过程中起到负向调节作用,通过促进炎症反应和纤维化进程,延缓修复。提示TRPV4可作为潜在的治疗靶点,被抑制后可能加速种植体周围软组织愈合并减轻纤维化。

关键词: 瞬时受体电位香草素4, 软组织愈合, 纤维化, 种植体, YAP/TEAD信号通路, 炎症反应

Abstract: PURPOSE: To investigate the effect of transient receptor potential vanilloid 4(TRPV4) on the healing of fibroblasts around the implant under different conditions, and to explore the regulatory mechanism of TRPV4 in the process of inflammation and fibrosis. METHODS: In vitro, mouse fibroblasts were randomly divided into three groups, i.e., NC group (cultured on ordinary 6-well plate), B14 group (cultured on 6-well plate hard matrix glass), BH14 group (cultured on glass plate with TRPV4 inhibitor HC-067047), and the expression level of TRPV4 was detected by PCR. TRPV4 gene knockout mice [TRPV4(-/-) group, n=20] and wild-type TRPV4 mice [TRPV4 (+/+) group, n=20] were used to establish the model of implant in vivo. The mice were randomly divided into two subgroups: implant group and peri-implantitis group. The soft tissue healing around the implant was observed at different time points after operation. Micro-CT scan was used to evaluate the osseointegration of implants. The inflammatory infiltration and soft tissue damage around the implant were observed by HE staining. The changes of collagen fibers in each group were detected by Masson staining. The expression of macrophage CD68 and myofibroblasts (α-SMA) was detected by IHF. PCR and ELISA were used to detect the expression levels of related inflammatory factors. The changes of epithelial structure, fibroblasts and extracellular matrix were observed under transmission electron microscope. RESULTS: The soft tissue repair of TRPV4(+/+) mice was slower than that of TRPV4(+/+) mice from 7 days to 30 days after implantation, with persistent inflammation and obvious fibrosis. TRPV4(-/-) mice showed faster soft tissue healing, significantly reduced inflammation and lower fibrosis. Consistent findings were observed after 30 days. IHF results showed that TRPV4 promoted macrophage activation and fibroblasts to myofibroblasts (a-SMA) transformation under inflammatory conditions, which promoted fibrosis progression. The correlation between the expression of TRPV4 and the expression levels of YAP/TEAD related proteins was observed, suggesting that TRPV4 may regulate the fibrosis process through the YAP/TEAD signaling pathway. CONCLUSIONS: TRPV4 plays a negative regulatory role in the healing process of peri-implant soft tissue by promoting inflammation and fibrosis. The results suggest that TRPV4 can be used as a potential therapeutic target, and inhibition of TRPV4 may accelerate the healing of peri-implant soft tissue and reduce fibrosis.

Key words: TRPV4, Soft tissue healing, Fibrosis, Implant, YAP/TEAD signaling pathway, Inflammatory response

中图分类号:

R782.13

史忠涛, 邱丹, 孙小娟, 陈志兵, 王诗涵, 张宇雄, 张丽. TRPV4对种植体周围纤维组织形成的调控作用[J]. 上海口腔医学, 2026, 35(4): 348-358.

Shi Zhongtao, Qiu Dan, Sun Xiaojuan, Chen Zhibing, Wang Shihan, Zhang Yuxiong, Zhang Li. The effect of TRPV4 on the formation of fibrous tissue around the implant[J]. Shanghai Journal of Stomatology, 2026, 35(4): 348-358.

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