RANK-L expression in Staphylococcus aureus- induced osteomyelitis, therapeutic intervention using nanotechnology and use of UV-killed bacteria as an osteoconductive coating for biomaterials.

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Somayaji, S. (2009). RANK-L expression in Staphylococcus aureus- induced osteomyelitis, therapeutic intervention using nanotechnology and use of UV-killed bacteria as an osteoconductive coating for biomaterials. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

Staphylococcus aureus is responsible for approximately 80% of all cases of human osteomyelitis. RANK-L is an essential signal produced by osteoblasts and is required for full osteoclastic differentiation. PGE2 - induced bone resorption involves both inducible cyclooxygenase (COX-2), as well as RANK-L. Our studies show that during infection with S. aureus, osteoblasts increase RANK-L and PGE2 secretion. Through the use of NS-398, a specific COX-2 inhibitor, we show that when PGE2 production is inhibited, RANK-L production is decreased. In the current study, we also demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin antibiotic. While titanium alloys are the preferred material of choice for orthopaedic implants, they do not mediate osseointegration (intimate apposition of bone to the implant surface). Enhancement of titanium (Ti) based biomaterials is therefore necessary to increase the functional lifespan of an implant. S. aureus can bind to biomaterials directly and also attach efficiently to osteoblasts. Moreover, as UV-killed S. aureus does not stimulate immune modulator expression, we investigated whether UV-killed bacteria could serve as a novel osteoconductive coating on Ti alloy surfaces. Our in vitro data demonstrate that osteoblast adhesion and matrix synthesis was enhanced on Ti surfaces coated with bacteria compared to uncoated surfaces. In vivo, the osteoconductivity of S. aureus-coated implants was increased at 8 weeks compared to the uncoated implants.

Details
Author

Somayaji, Shankari

Title

RANK-L expression in Staphylococcus aureus- induced osteomyelitis, therapeutic intervention using nanotechnology and use of UV-killed bacteria as an osteoconductive coating for biomaterials.

Physical Description

1 online resource (151 pages) : PDF

Date

2009

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

Staphylococcus aureus is responsible for approximately 80% of all cases of human osteomyelitis. RANK-L is an essential signal produced by osteoblasts and is required for full osteoclastic differentiation. PGE2 - induced bone resorption involves both inducible cyclooxygenase (COX-2), as well as RANK-L. Our studies show that during infection with S. aureus, osteoblasts increase RANK-L and PGE2 secretion. Through the use of NS-398, a specific COX-2 inhibitor, we show that when PGE2 production is inhibited, RANK-L production is decreased. In the current study, we also demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin antibiotic. While titanium alloys are the preferred material of choice for orthopaedic implants, they do not mediate osseointegration (intimate apposition of bone to the implant surface). Enhancement of titanium (Ti) based biomaterials is therefore necessary to increase the functional lifespan of an implant. S. aureus can bind to biomaterials directly and also attach efficiently to osteoblasts. Moreover, as UV-killed S. aureus does not stimulate immune modulator expression, we investigated whether UV-killed bacteria could serve as a novel osteoconductive coating on Ti alloy surfaces. Our in vitro data demonstrate that osteoblast adhesion and matrix synthesis was enhanced on Ti surfaces coated with bacteria compared to uncoated surfaces. In vivo, the osteoconductivity of S. aureus-coated implants was increased at 8 weeks compared to the uncoated implants.

Genre

doctoral dissertations

Subjects--Topics

Microbiology

Degree

Ph.D.

Keywords

Biomaterials
Nanoparticles
Osteoblasts
Osteomyelitis
RANK-L
Staphylococcus Aureus

Subject Area

Biology

Advisor(s)

Hudson, Michael

Committee Members

Bost, Kenneth
Marriott, Ian
Schrum, Laura
Huet, Yvette
Ogle, Craig

Degree Note

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2009.

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Rights Holder Information

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Identifier

Somayaji_uncc_0694D_10019

Permalink

http://hdl.handle.net/20.500.13093/etd:41