Journal
STEM CELLS
Volume 33, Issue 2, Pages 615-621Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.1858
Keywords
Marrow stromal stem cells; Mesenchymal stem cells; Calcium flux; Differentiation and mechanosensation
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Funding
- National Natural Science Foundation of China [81170936, 81370203]
- 973 Major State Basic Research Development Program of China [2011CB809101]
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Mesenchymal stem cells (MSCs) are multipotential stem cells residing in the bone marrow. Several studies have shown that mechanical stimulation modulates MSC differentiation through mobilization of second messengers, but the mechanism of mechanotransduction remains poorly understood. In this study, using fluorescence and laser confocal microcopy as well as patch-clamp techniques, we identified the transient receptor potential melastatin type 7 (TRPM7) channel as the key channel involved in mechanotransduction in bone marrow MSCs. TRPM7 knockdown completely abolished the pressure-induced cytosolic Ca2+ increase and pressure-induced osteogenesis. TRPM7 directly sensed membrane tension, independent of the cytoplasm and the integrity of cytoskeleton. Ca2+ influx through TRPM7 further triggered Ca2+ release from the inositol trisphosphate receptor type 2 on the endoplasmic reticulum and promoted NFATc1 nuclear localization and osteogenesis. These results identified a central role of TRPM7 in MSC mechanical stimulation-induced osteogenesis.
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