title: Brief reports: TRPM7 Senses mechanical stimulation inducing osteogenesis in human bone marrow mesenchymal stem cells.
abstract: 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 Ca(2+) increase and pressure-induced osteogenesis. TRPM7 directly sensed membrane tension, independent of the cytoplasm and the integrity of cytoskeleton. Ca(2+) influx through TRPM7 further triggered Ca(2+) 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: E
authors.initials: E
authors.lastname: Xiao
authors.forename: H Q
authors.initials: HQ
authors.lastname: Yang
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Gan
authors.forename: Deng-Hui
authors.initials: DH
authors.lastname: Duan
authors.forename: Lin-Hai
authors.initials: LH
authors.lastname: He
authors.forename: YunBo
authors.initials: Y
authors.lastname: Guo
authors.forename: S Q
authors.initials: SQ
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D011312:Pressure; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human
keywords: Calcium flux; Differentiation and mechanosensation; Marrow stromal stem cells; Mesenchymal stem cells