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TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9: A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION

Mbimba, Thomas S, Jr
http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594

Abstract Details

2015, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
In the present studies, we sought to understand the regulatory function of Trafficking protein particle complex 9 (TRAPPC9) in both osteoblast and osteoclast using in vivo and in vitro approaches. Furthermore, we wanted to determine the signal mechanism responsible for TRAPPC9-mediated function in bone cells. To that end, we utilized a loss of and gain of function approaches using the lentiviral vector system to downregulate or over-express TRAPPC9, respectively. Lastly, we evaluated the role of TRAPPC9 in two in vivo models using critical size defect for bone regeneration to evaluate osteoblast function and a calvaria osteolysis model for bone resorption to evaluate osteoclast function. Our overall premise is that TRAPPC9 is a negative regulator of osteoblast differentiation and its down-regulation enhances osteoblast differentiation and function on the other, hand TRAPPC9 is a positive regulator of osteoclast differentiation and function and its expression enhances osteoclast mediated bone resorption. Our results show that TRAPPC9 inhibition greatly enhances osteoblast differentiation and function in both Mesenchymal stem cells and osteoblast like MC3T3-E1 cell line in vivo and in vivo examination also showed an enhanced bone regeneration properties in animal treated with TRAPPC9 shRNA lentivirus. This inhibition was mediated through the activation of NF-¿B. Result also showed that TRAPPC9 inhibition showed suppressed cell proliferation by inhibiting cell cycle progression in both cell types. In osteoclast however, TRAPPC9 inhibition showed opposite effects; TRAPPC9 over-expression enhanced RANKL-induced osteoclast differentiation and function in vitro. In vivo experiment also showed that calvaries treated with lentiviral particles overexpressing TRAPPC9 enhanced RANKL-induced calvaria osteolysis. This inhibition was also mediated through the inhibition of NF-¿B activation. These data suggest that TRAPPC9 expression is important for both osteoblast and osteoclast differentiation and function. Our data also suggest that TRAPPC9 could be a potential target for therapeutic treatment of bone loss and improved fracture recovery.
Fayez Safadi (Committee Chair)
Walter Horton, Jr. (Committee Member)
James Hardwick (Committee Member)
William Lynch (Committee Member)
Min-Ho Kim (Other)
Hanbin Mao (Other)
278 p.
Biomedical Research; Cellular Biology; Molecular Biology

Recommended Citations

Citations

  • Mbimba, Jr, T. S. (2015). TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9: A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594

    APA Style (7th edition)

  • Mbimba, Jr, Thomas. TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9: A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION. 2015. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594.

    MLA Style (8th edition)

  • Mbimba, Jr, Thomas. "TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9: A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION." Doctoral dissertation, Kent State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594

    Chicago Manual of Style (17th edition)

kent1448841594
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© 2015, some rights reserved.Creative Commons License TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9: A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION by Thomas S Mbimba Jr is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Kent State University and OhioLINK.