Microdamage induced calcium efflux from bone matrix activates intracellular calcium signaling in osteoblasts via L-type and T-type voltage-gated calcium channels |
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| Affiliation: | 1. Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA;2. Department of Orthopedics, Case Western Reserve University, Cleveland, OH 44106, USA;3. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA;1. Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany;2. Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Germany;3. Electron Microscopy Facility, Center for Regenerative Therapies Dresden, Germany;4. Dermatology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA;5. DFG Research Center for Regenerative Therapies Dresden, Germany;1. College of Kinesiology, University of Saskatchewan, Saskatoon, SK, Canada;2. Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada;3. College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;4. Saskatoon Osteoporosis and CaMos Centre, Saskatoon, SK, Canada;1. Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada;2. Faculty of Dentistry, McGill University, Montreal, Quebec, Canada;3. Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada;1. Hugo W. Moser Research Institute at Kennedy Krieger, Inc., 707 North Broadway, Baltimore, MD 21205, USA;2. Hospital for Special Surgery, Mineralized Tissue Laboratory 535 E 70th Street, New York, NY 10021, USA;3. Geriatric Medicine and Gerontology, Johns Hopkins Medical Institutions, Room 1A-12 JHAAC, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA;1. Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA;2. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA;1. Institute of Animal Physiology and Genetics CAS, v.v.i., Brno, Czech Republic;2. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic;3. Department of Physiology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic;4. Institute of Anatomy, Charles University, Prague, Czech Republic;5. Department of Craniofacial Development and Stem Cell Biology, King''s College London, London, UK;6. Department of Anatomy, Histology and Embryology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic |
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| Abstract: | Mechanisms by which bone microdamage triggers repair response are not completely understood. It has been shown that calcium efflux ([Ca2 +]E) occurs from regions of bone undergoing microdamage. Such efflux has also been shown to trigger intracellular calcium signaling ([Ca2 +]I) in MC3T3-E1 cells local to damaged regions. Voltage-gated calcium channels (VGCCs) are implicated in the entry of [Ca2 +]E to the cytoplasm. We investigated the involvement of VGCC in the extracellular calcium induced intracellular calcium response (ECIICR). MC3T3-E1 cells were subjected to one dimensional calcium efflux from their basal aspect which results in an increase in [Ca2 +]I. This increase was concomitant with membrane depolarization and it was significantly reduced in the presence of Bepridil, a non-selective VGCC inhibitor. To identify specific type(s) of VGCC in ECIICR, the cells were treated with selective inhibitors for different types of VGCC. Significant changes in the peak intensity and the number of [Ca2 +]I oscillations were observed when L-type and T-type specific VGCC inhibitors (Verapamil and NNC55-0396, respectively) were used. So as to confirm the involvement of L- and T-type VGCC in the context of microdamage, cells were seeded on devitalized notched bone specimen, which were loaded to induce microdamage in the presence and absence of Verapamil and NNC55-0396. The results showed significant decrease in [Ca2 +]I activity of cells in the microdamaged regions of bone when L- and T-type blockers were applied. This study demonstrated that extracellular calcium increase in association with damage depolarizes the cell membrane and the calcium ions enter the cell cytoplasm by L- and T-type VGCCs. |
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