title: Shear stress-induced Ca(2+) elevation is mediated by autocrine-acting glutamate in osteoblastic MC3T3-E1 cells.
abstract: Mechanical loading is an important regulatory factor in bone homeostasis. Neurotransmitters, such as glutamate and ATP, are known to be released from osteoblasts, but their roles have been less studied. In this study, we investigated the role of transmitter release in mechanotransduction. To identify from where transmitters were released, focal fluid flow was applied to a single cell of MC3T3-E1, mouse calvaria-derived osteoblastic cell line, by using a glass micropipette. Intracellular Ca(2+) elevation induced by the focal shear stress was eliminated by either GdCl3, a mechanosensing channel inhibitor, or removal of extracellular Ca(2+). On the other hand, the focal shear stress-induced Ca(2+) elevation was also significantly suppressed by inositol triphosphate receptor antagonist or vesicular release inhibitors. These results suggest that not only mechanosensitive channel-mediated Ca(2+) influx but also some autocrine transmitters are involved in mechanotransduction. Additionally, glutamate receptor antagonists, but not ATP receptor antagonist, suppressed most of the focal shear stress-induced Ca(2+) elevation. Therefore, it is suggested that glutamate is released from osteoblasts following the activation of mechanosensitive Ca(2+) channels and acts in an autocrine manner. The glutamate release may have a significant role in the initial event of mechanotransduction in bone tissue.
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan; Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan.
authors.forename: Norika
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kodama
authors.affiliation: Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Goto
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan. Electronic address: togariaf@dpc.aichi-gakuin.ac.jp.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Togari
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D001842:Bone and Bones / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005971:Glutamates / Q000378:metabolism / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D005971:Glutamates; D018377:Neurotransmitter Agents; D002118:Calcium
keywords: Autocrine; Glutamate; Mechanotransduction; Osteoblast; Shear stress