Early molecular assessment of osseointegration in humans
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41446 | GEO | 2013/09/17
SECONDARY ACCESSION(S): PRJNA177030
REPOSITORIES: GEO
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Project description: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.
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Project description:Optimizing the immune microenvironment is essential for successful implant osseointegration. In this study, four different nano/microstructures were fabricated on polyetheretherketone (PEEK) substrates by varying the agitation speed during sulfonation to influence osteoimmunomodulation and implant integration. The results indicate that nano/microstructures with minimal dimensions (SP450) inhibit actin polymerization by reducing calcium influx through Piezo1, activating the anti-inflammatory M2 macrophage phenotype. Among the tested specimens, SP450 exhibited the lowest expression levels of tumor necrosis factor-α and interleukin-1β while releasing the highest levels of anti-inflammatory factors, including interleukin-4 and interleukin-10. This optimized immune environment promotes the osteogenesis of MC3T3-E1 pre-osteoblasts and enhances the osseointegration of PEEK implants. Transcriptomic analysis and validation experiment further revealed that SP450 inhibits osteoclastic differentiation by down-regulating transforming growth factor-β2 and suppressing the NF-κB signaling pathway. These findings suggest that manipulating the surface topography of PEEK implants is an effective strategy for enhancing osseointegration with promising clinical applications.
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Project description:Exosomes are nanoscale extracellular vesicles. Several studies have shown that exosomes participate in intercellular communication and play a key role in osseointegration. However, it is unclear whether exosomes and their contents participate in the communication between the immune and skeletal systems in the process of osseointegration. In this study, we obtained smooth titanium disks by polishing and micro-/nano-texture hierarchical topography titanium disks by sandblasted large-grit acid-etched (SLA) technology combined with alkali thermal reaction. After stimulating rat RAW264.7 cells with these two kinds of titanium disks, we co-cultured the MC3T3-E1 cells and the RAW264.7 cells, obtained and identified the exosomes derived from RAW264.7 cells, and studied the effect of the osteoimmune microenvironment and the exosomes on the osseointegration of rat MC3T3-E1 cells. Cell counting kit-8 (CCK-8), real time quantitative PCR, western blotting, alizarin red staining, and quantitative and confocal fluorescence microscopy were used to study the effects of exosomes on MC3T3-E1 cells; RNA sequencing and correlation analysis were performed. We found that the osteoimmune microenvironment could promote the osseointegration of MC3T3-E1 cells. We successfully isolated exosomes and found that RAW264.7 cell-derived exosomes can promote osteogenic differentiation and mineralization of MC3T3-E1 cells. Through RNA sequencing and gene analysis, we found differentially expressed microRNAs that targeted the signal pathways that may be related, such as mTOR, AMPK, Wnt, etc, and thus provide a reference for the mechanism of osteoimmunue regulation of implant osseointegration. The study further elucidated the mechanism of implant osseointegration and provided new insights into the effect of exosomes on implant osseointegration, and provided reference for clinical improvement of implant osseointegration and implant success rate.
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Project description:Mechanism of exosomes involved in osteoimmunity promoting osseointegration around titanium implants with micro-/nano-texture hierarchical topography
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Project description:Objective: to identify the early molecular processes involved in osseointegration associated with a micro roughened and nanosurface featured implants. Thirty-two titanium implants with surface topographies exhibiting nanoscale features (AT-I) and microrough surface without nanoscale features (AT-II) were placed in the tibiae of 8 rats and subsequently harvested at 2 and 4 days after placement. Total RNA was isolated from cells adherent to retrieved implants. A whole genome microarray using the Affymetrix Rat gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces.
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Project description:In this study we want to ascertain the differences and similarities of infected and inflammated peri implant tissue versus healthy peri implant tissue at the mRNA level. Six of the patients where affected by periimplantitis. In situ dental implants where explanted because of inflammation and non-integration. From two patients, implants were explanted because of wrong placement. They where classified as implants with healthy periimplant tissue.
2014-05-14 | E-GEOD-57631 | biostudies-arrayexpress
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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Project description:The poor osseointegration of dental implants in diabetic patients has become a long-standing clinical problem. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes vascularized osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants sucessfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data proved that Mg2+ promoted vascularized osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
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