The effect of TRPV4 on the formation of fibrous tissue around the implant

doi:10.19439/j.sjos.2026.04.002

Abstract

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

CLC Number:

R782.13

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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