Unknown,Transcriptomics,Genomics,Proteomics

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Early molecular assessment of osseointegration in humans

ABSTRACT: To determine the early temporal wide genome transcription regulation by the surface topography at the bone-implant interface of implants bearing micro-roughened or superimposed nanosurface topology. Fourty four cp titanium implants with surface topographies exhibiting nanoscale features (Osseospeed-OS) and microrough surface without nanoscale features (TiOblast-TiO) were placed in the alveolar bone of 11 systemically healthy subjects and subsequently harvested at 3 and 7 days after placement. Total RNA was isolated from cells adherent to retrieved implants. A whole genome microarray using the Affymetrix Human gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces.

ORGANISM(S): Homo sapiens

SUBMITTER: Lyndon Cooper

PROVIDER: E-GEOD-41446 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of β-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors’ knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway. PLGA implants with +/- incorporated Li were inserted in rat tibia for 7 or 28 days, peri-implant bone was harvested and RNA extracted using Qiazol lysis reagent and TissueLyser followed by Qiagen's Rneasy Micro Kit. The microarray experiment was conducted at SCIBLU Genomics (www.lu.se/sciblu) according to Affymetrix guidelines (n=6).

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Early molecular assessment of osseointegration in humans

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