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dc.contributor.authorFang, Mimien_US
dc.date.accessioned2009-01-22T15:37:00Z
dc.date.available2009-01-22T15:37:00Z
dc.date.issued2008-11-19en_US
dc.identifier.urihttp://hdl.handle.net/1853/26462
dc.description.abstractBiomaterial surface properties such as microtopography and energy can change cellular responses at the cell-implant interface. Phospholipase D (PLD) is required for differentiation of osteoblast-like MG63 cells on machined and grit-blasted titanium surfaces. Here, we determined if PLD is also required on microstructured/high-energy substrates and the mechanism involved. shRNAs for human PLD1 and PLD2 were used to silence MG63 cells. Wild-type and PLD1 or PLD1/2 silenced cells were cultured on smooth-pretreatment surfaces (PT); grit-blasted, acid-etched surfaces (SLA); and SLA surfaces modified to have higher surface energy (modSLA). PLD was inhibited with ethanol or activated with 24,25-dihydroxyvitamin-D₃ [24R,25(OH)₂D₃]. As surface roughness/energy increased, PLD mRNA and activity increased, cell number decreased, osteocalcin and osteoprotegerin increased, and protein kinase C (PKC) and alkaline phosphatase specific activities increased. Ethanol inhibited PLD and reduced surface effects on these parameters. There was no effect on these parameters after knockdown of PLD1, but PLD1/2 double knockdown had effects comparable to PLD inhibition. 24R,25(OH)₂D₃increased PLD activity and production of osteocalcin and osteoprotegerin, but decreased cell number on the rough/high-energy surfaces. These results confirm that surface roughness/energy-induced PLD activity is required for osteoblast differentiation and that PLD2 is the main isoform involved in this pathway. Here we showed that PLD is activated by 24R,25(OH)₂D₃ in a surface-dependent manner and inhibition of PLD reduced the effects of surface microstructure/energy on PKC, suggesting that PLD mediates the stimulatory effect of microstructured/high-energy surfaces via PKC-dependent signaling.en_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectOsteoblastsen_US
dc.subjectPhospholipase Den_US
dc.subjectTitanium implantsen_US
dc.subjectSurface energyen_US
dc.subject.lcshBiomedical materials
dc.subject.lcshSurface roughness
dc.subject.lcshImplants, Artificial Physiological effect
dc.subject.lcshPhospholipases
dc.titleThe role of phospholipase d in osteoblasts in response to titanium surfacesen_US
dc.typeThesisen_US
dc.description.degreeM.S.en_US
dc.contributor.departmentBiomedical Engineeringen_US
dc.description.advisorCommittee Chair: Boyan, Barbara; Committee Member: Eskin, Suzanne; Committee Member: Lobachev, Kirill; Committee Member: Schwartz, Zvien_US


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