title: Dynamic fluid flow induced mechanobiological modulation of in situ osteocyte calcium oscillations.
abstract: Distribution of intramedullary pressure (ImP) induced bone fluid flow has been suggested to influence the magnitude of mechanotransductory signals within bone. As osteocytes have been suggested as major mechanosensors in bone network, it is still unclear how osteocytes embedded within a mineralized bone matrix respond to the external mechanical stimuli derived from direct coupling of dynamic fluid flow stimulation (DFFS). While in vitro osteocytes show unique Ca(2+) oscillations to fluid shear, the objective of this study was to use a confocal imaging technique to visualize and quantify Ca(2+) responses in osteocytes in situ under DFFS into the marrow cavity of an intact ex vivo mouse femur. This study provided significant technical development for evaluating mechanotransduction mechanism in bone cell response by separation of mechanical strain and fluid flow factors using ImP stimulation, giving the ability for true real-time imaging and monitoring of bone cell activities during the stimulation. Loading frequency dependent Ca(2+) oscillations in osteocytes indicated the optimized loading at 10Hz, where such induced response was significantly diminished via blockage of the Wnt/β-catenin signaling pathway. The results provided a pilot finding of the potential crosstalk or interaction between Wnt/β-catenin signaling and Ca(2+) influx signaling of in situ osteocytes in response to mechanical signals. Findings from the present study make a valuable tool to investigate how in situ osteocytes respond and transduce mechanical signals, e.g. DFFS, as a central mechanosensor.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States.
authors.forename: Minyi
authors.initials: M
authors.lastname: Hu
authors.affiliation: CMIC-Two Photon Imaging Center, Stony Brook University, Stony Brook, NY 11794-5200, United States.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Tian
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Gibbons
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States. Electronic address: Yi-Xian.Qin@stonybrook.edu.
authors.forename: Yi-Xian
authors.initials: YX
authors.lastname: Qin
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D005260:Female; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010011:Osteocytes / Q000166:cytology / Q000502:physiology*; D012212:Rheology / Q000379:methods; D033081:Shear Strength / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D002118:Calcium
keywords: Bone fluid flow; Calcium homeostasis; Calcium signaling; Mechanotransduction; Osteocyte; Wnt signaling