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RESPONSE OF BONE CELLS TO DIFFUSE MICRODAMAGE INDUCED CALCIUM EFFLUX.pdf (32.54 MB)
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RESPONSE OF BONE CELLS TO DIFFUSE MICRODAMAGE INDUCED CALCIUM EFFLUX
Author Info
Jung, Hyungjin
ORCID® Identifier
http://orcid.org/0000-0002-1942-5557
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case1496519515579907
Abstract Details
Year and Degree
2017, Doctor of Philosophy, Case Western Reserve University, EMC - Mechanical Engineering.
Abstract
Daily physiological activity may induce two modes of damage to bone matrix: compression-induced linear microcrack, or tension-induced diffuse microdamage. The repair process of linear microcrack is initiated by osteocyte apoptosis, followed by basic multicellular unit activation for damage removal and new bone formation. However, the mechanism by which bone cells detect diffuse microdamage and actively mediate its repair is not yet fully understood. Previous studies have proposed that mechanical stretch or fluid shear around the damaged region may stimulate reparative functions of bone cells. We have proposed extracellular calcium ([Ca2+]E) efflux from damaged bone matrix as a novel mechanism which initiates damage repair functions of bone cells. An early study from our group reported increased [Ca2+]E on diffuse microdamage upon post- yield loading. The [Ca2+]E efflux, named diffuse microdamage induced calcium efflux (DMICE), was reported to activate intracellular calcium ([Ca2+]I) signaling in osteoblasts. We hypothesized that DMICE plays an essential role in repair of diffuse microdamage, given that elevated [Ca2+]E concentration has been reported to activate [Ca2+]I signaling in osteoblasts, followed by increased expression of osteogenic-related transcription factors, and ultimately enhanced protein synthesis and mineralization. Therefore, DMICE was hypothesized as a cue which initiates downstream pathways of [Ca2+]I signaling in ¿xvi osteoblasts, which consequently triggers osteoblast-mediated restoration of damaged bone. This study investigated the role of DMICE as an initiator of bone repair. The key findings from this study were as follows: 1) there was spatial proximity between diffuse microdamage and local activation of [Ca2+]I signaling, 2) Voltage gated calcium channels (VGCC), specifically L-type and T-type, VGCC were involved in extracellular calcium induced intracellular calcium response, 3) DMICE activated anabolic responses of osteoblasts for diffuse microdamage repair, and 4) repetitive short-span application of [Ca2+]E showed therapeutic potential for bone healing. These outcomes provide further insight into how osteoblasts respond to diffuse microdamage for damage repair. Such findings will help to improve modern medical interventions to treat bone diseases and to reduce bone fracture incidence. Additionally, the knowledge gained from the dose and treatment regimen of calcium therapy is important in the setting of guidelines for developing approaches to treat fractures.
Committee
Ozan Akkus (Committee Chair)
Clare Rimnac (Committee Member)
Eben Alsberg (Committee Member)
Umut Gurkan (Committee Member)
Pages
192 p.
Subject Headings
Biomechanics
;
Mechanical Engineering
Keywords
Bone microdamage, Osteoprogenitor cells, Voltage-gated calcium channel, Intracellular calcium signaling, Bone formation,
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Mendeley
Citations
Jung, H. (2017).
RESPONSE OF BONE CELLS TO DIFFUSE MICRODAMAGE INDUCED CALCIUM EFFLUX
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1496519515579907
APA Style (7th edition)
Jung, Hyungjin.
RESPONSE OF BONE CELLS TO DIFFUSE MICRODAMAGE INDUCED CALCIUM EFFLUX.
2017. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case1496519515579907.
MLA Style (8th edition)
Jung, Hyungjin. "RESPONSE OF BONE CELLS TO DIFFUSE MICRODAMAGE INDUCED CALCIUM EFFLUX." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1496519515579907
Chicago Manual of Style (17th edition)
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Document number:
case1496519515579907
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Copyright Info
© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.