TRPC1 channel modulates mechanical stretch-induced bone marrow mesenchymal stem cell proliferation through...

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.