TRPC1 channel modulates mechanical stretch-induced bone marrow mesenchymal stem cell proliferation through Ca²⁺-dependent ERK1/2 activation

Junqi Men¹, Yangbi Huang², Chuyan Shi³, Xinlan Chen¹, Juncheng Bai¹, Hui Shao¹, Yingying Guo¹, Xing Chen¹, Lin-Hua Jiang⁴, Xiaoling Jia⁵, Huawei Liu⁶

Affiliations

¹ Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering and with the School of Engineering Medicine, Beihang University, Beijing, China.
² Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering and with the School of Engineering Medicine, Beihang University, Beijing, China; Fujian Maternity and Child Health Hospital, Fuzhou, China.
³ Department of Stomatology Medical School of Chinese PLA The First Medical Center Chinese PLA General Hospital, Beijing, China.
⁴ Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, and Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, China; Henan Key Laboratory of Neurorestoratology and Protein Modification, Henan Medical University, Xinxiang, China. Electronic address: jianglinhua@xxmu.edu.cn.
⁵ Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering and with the School of Engineering Medicine, Beihang University, Beijing, China. Electronic address: jiaxiaoling@buaa.edu.cn.
⁶ Department of Stomatology Medical School of Chinese PLA The First Medical Center Chinese PLA General Hospital, Beijing, China. Electronic address: liuhuawei840222@126.com.

PMID: 42030623
DOI: 10.1016/j.ceca.2026.103137

Abstract

Mesenchymal stem cells (MSCs) are highly promising for regenerative medicine, but their limited proliferating capability hinders clinical applications. While mechanical stretch induces MSC proliferation, the underlying mechanisms remain unclear. In this study, we identified a novel role of the transient receptor potential canonical 1 (TRPC1) channel in mechanical stretch-induced Ca²⁺ signaling in MSCs. Exposure of rat bone marrow-derived MSCs (BMSCs) to 10% static stretch induced upregulation of the TRPC1 expression coupled with enhancement of BMSC proliferation, which was inhibited by TRPC1 knockdown. Stretch also induced an increase in intracellular Ca²⁺ concentration, which was decreased by TRPC1 knockdown or extracellular Ca²⁺chelation. Consistently, stretch-induced BMSC proliferation was suppressed by extracellular or intracellular Ca²⁺chelation. In addition, stretch induced activation of extracellular regulated protein kinase 1/2 (ERK1/2), which was attenuated by TRPC1 knockdown or intracellular Ca²⁺chelation. Finally, stretch-induced BMSC proliferation was suppressed by ERK1/2 inhibition. Collectively, these results suggest that the TRPC1 channel mediates mechanical stretch-induced modulation of BMSC proliferation by regulating Ca²⁺-dependent ERK1/2 activation. This finding provides new mechanistic insights into mechanical stimulation of MSC proliferation and also a viable bioengineering strategy to promote MSC proliferation.

Keywords: BMSC; Ca(2+); Cell proliferation; ERK; Mechanical stretch; TRPC1 channel.

Cell Calcium. 2026 Apr 19:135:103137.doi: 10.1016/j.ceca.2026.103137.

TRPC1 channel modulates mechanical stretch-induced bone marrow mesenchymal stem cell proliferation through Ca2+-dependent ERK1/2 activation

Abstract

近期文章

TRPC1 channel modulates mechanical stretch-induced bone marrow mesenchymal stem cell proliferation through Ca²⁺-dependent ERK1/2 activation