Intestinal Epithelial Piezo1–Serotonin Signaling Contributes to Vascular Injury in Steroid-Induced Osteonecrosis of the Femoral Head
- 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
- 2Division of Gastroenterology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract
Steroid-induced osteonecrosis of the femoral head (SONFH) develops with early microvascular injury, but the systemic signals connecting glucocorticoid exposure to the femoral head remain incompletely defined. We examined whether intestinal epithelial Piezo1–TPH1–serotonin signaling contributes to this process. A glucocorticoid-induced SONFH model was studied in male C57BL/6 mice (8–10 weeks old), using pharmacological inhibition of peripheral serotonin synthesis, intestinal epithelial-specific Piezo1 deletion, micro-computed tomography, histological and vascular analyses, bone microvascular endothelial cell (BMEC) assays, and independent public transcriptomic datasets. Glucocorticoid exposure increased intestinal Piezo1 and TPH1 expression and circulating serotonin, together with loss of CD31hiEMCNhi type H vessels and trabecular deterioration. Inhibiting peripheral serotonin synthesis reduced vascular and structural injury. Intestinal epithelial Piezo1 deletion blunted TPH1 upregulation, preserved femoral-head microvasculature, and improved trabecular architecture. In BMECs, serotonin impaired tube formation and increased Bax-, Caspase-3-, and NLRP3-associated signaling; intestinal Piezo1 deletion reduced the corresponding injury signals in vivo. Intestinal epithelial Piezo1–TPH1–serotonin signaling therefore contributes to SONFH-associated microvascular injury in this model.
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BibTeX
@article{han2026intestinal,
title = {{Intestinal Epithelial Piezo1–Serotonin Signaling Contributes to Vascular Injury in Steroid-Induced Osteonecrosis of the Femoral Head}},
author = {Lizhi Han and Yuxi Wang and Ping Wang and Yihao Tao and Bo Wang and Xiao Lv and Tao Bai and Yong Feng},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209213},
url = {https://www.mdpi.com/1422-0067/27/20/9213},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intestinal Epithelial Piezo1–Serotonin Signaling Contributes to Vascular Injury in Steroid-Induced Osteonecrosis of the Femoral Head
AU - Lizhi Han
AU - Yuxi Wang
AU - Ping Wang
AU - Yihao Tao
AU - Bo Wang
AU - Xiao Lv
AU - Tao Bai
AU - Yong Feng
PY - 2026
DA - 2026/10/16
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209213
UR - https://www.mdpi.com/1422-0067/27/20/9213
AB - Steroid-induced osteonecrosis of the femoral head (SONFH) develops with early microvascular injury, but the systemic signals connecting glucocorticoid exposure to the femoral head remain incompletely defined. We examined whether intestinal epithelial Piezo1–TPH1–serotonin signaling contributes to this process. A glucocorticoid-induced SONFH model was studied in male C57BL/6 mice (8–10 weeks old), using pharmacological inhibition of peripheral serotonin synthesis, intestinal epithelial-specific Piezo1 deletion, micro-computed tomography, histological and vascular analyses, bone microvascular endothelial cell (BMEC) assays, and independent public transcriptomic datasets. Glucocorticoid exposure increased intestinal Piezo1 and TPH1 expression and circulating serotonin, together with loss of CD31hiEMCNhi type H vessels and trabecular deterioration. Inhibiting peripheral serotonin synthesis reduced vascular and structural injury. Intestinal epithelial Piezo1 deletion blunted TPH1 upregulation, preserved femoral-head microvasculature, and improved trabecular architecture. In BMECs, serotonin impaired tube formation and increased Bax-, Caspase-3-, and NLRP3-associated signaling; intestinal Piezo1 deletion reduced the corresponding injury signals in vivo. Intestinal epithelial Piezo1–TPH1–serotonin signaling therefore contributes to SONFH-associated microvascular injury in this model.
SN - 1422-0067
ER -