Gene expression profiling of cells involved in periodontal regeneration.

Understanding the molecular mechanisms involved in periodontal regeneration is important for the development of more predictable clinical techniques. This study aimed to identify these mechanisms by comparing the gene expression profiles of cells derived from regenerating defects with patient-matched periodontal ligament cells. Gene profiling was carried out via Affymetrix U133A arrays containing probes for 22,000 genes. Robust differences in gene expression were obtained by identifying genes that consistently changed by a minimum of 2-fold. Analysis of molecular function as designated by gene ontology (GO) identified differentially regulated mechanisms including protein metabolism, tyrosine kinase activity, and skeletal development. The differentially expressed genes could be broadly divided into the categories of protein biosynthesis and turnover, structural constituents of the cytoskeleton and extracellular matrix, and signal transduction. The differential expression of 4 genes (EGR-1, elastin, osteoprotegerin, and IGFBP3) was confirmed via real-time polymerase chain reaction (PCR). Further, the expression of another 2 differentially expressed transcripts, decorin and biglycan, was immunohistochemically confirmed in a periodontal wound healing model and the protein expression was consistent with the pattern of gene expression. This study gives insight into the molecular processes involved in periodontal regeneration and identifies cell markers that are characteristic of regenerating periodontal tissues.

[1]  S. Ghosh,et al.  Role of nuclear factor‐κB in the immune system and bone , 2005 .

[2]  Q. Jin,et al.  Current concepts in periodontal bioengineering. , 2005, Orthodontics & craniofacial research.

[3]  C. Stuelten,et al.  Extracellular Matrix Proteoglycans Control the Fate of Bone Marrow Stromal Cells* , 2005, Journal of Biological Chemistry.

[4]  F. Graziani,et al.  Periodontal wound healing following GTR therapy of dehiscence-type defects in the monkey: short-, medium- and long-term healing. , 2005, Journal of clinical periodontology.

[5]  P. Sharpe,et al.  Expression of the Hedgehog antagonists Rab23 and Slimb/betaTrCP during mouse tooth development. , 2005, Archives of oral biology.

[6]  R. Teasdale,et al.  In Vivo Analysis of Growth Hormone Receptor Signaling Domains and Their Associated Transcripts , 2005, Molecular and Cellular Biology.

[7]  Guoying Liu,et al.  NetAffx Gene Ontology Mining Tool: a visual approach for microarray data analysis. , 2004, Bioinformatics.

[8]  P. Sharpe,et al.  Neural crest contribution to mammalian tooth formation. , 2004, Birth defects research. Part C, Embryo today : reviews.

[9]  M. Tonetti,et al.  Long-term tooth survival following regenerative treatment of intrabony defects. , 2004, Journal of periodontology.

[10]  P. Knaus,et al.  Signal transduction of bone morphogenetic protein receptors. , 2004, Cellular signalling.

[11]  Douglas A. Hosack,et al.  Identifying biological themes within lists of genes with EASE , 2003, Genome Biology.

[12]  Yan Zhou,et al.  Differential gene expression in the rat caudate putamen after “binge” cocaine administration: Advantage of triplicate microarray analysis , 2003, Synapse.

[13]  Wei-Min Liu,et al.  Robust estimators for expression analysis , 2002, Bioinform..

[14]  M. Bronner‐Fraser,et al.  Id4 expression and its relationship to other Id genes during avian embryonic development , 2001, Mechanisms of Development.

[15]  S. Ivanovski,et al.  Isolation and characterization of fibroblasts derived from regenerating human periodontal defects. , 2001, Archives of oral biology.

[16]  P. Bartold,et al.  The expression of plasminogen activator system in a rat model of periodontal wound healing. , 2001, Journal of periodontology.

[17]  S. Ivanovski,et al.  Expression of Bone Matrix Protein mRNAs by Primary and Cloned Cultures of the Regenerative Phenotype of Human Periodontal Fibroblasts , 2001, Journal of dental research.

[18]  S. Ivanovski,et al.  Expression of bone associated macromolecules by gingival and periodontal ligament fibroblasts. , 2001, Journal of periodontal research.

[19]  M. Braddock,et al.  Tissue repair with a therapeutic transcription factor. , 2000, Human gene therapy.

[20]  S. Ivanovski,et al.  An immunohistochemical study of matrix molecules associated with barrier membrane-mediated periodontal wound healing. , 2000, Journal of periodontal research.

[21]  H. Moses,et al.  Regulation of differentiation by TFG-β , 1996 .

[22]  W. Giannobile,et al.  Periodontal tissue engineering by growth factors. , 1996, Bone.

[23]  C. McCulloch,et al.  Periodontal ligament cell populations: The central role of fibroblasts in creating a unique tissue , 1996, The Anatomical record.

[24]  S. Dedhar,et al.  Constitutive expression of calreticulin in osteoblasts inhibits mineralization , 1995, The Journal of cell biology.

[25]  C. McCulloch,et al.  Cellular origins and differentiation control mechanisms during periodontal development and wound healing. , 1994, Journal of periodontal research.

[26]  M. Young,et al.  Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[27]  K. Warrer,et al.  Formation of a periodontal ligament around titanium implants. , 1990, Journal of periodontology.

[28]  T. Karring,et al.  Healing following implantation of periodontitis-affected roots into gingival connective tissue. , 1980, Journal of clinical periodontology.

[29]  T. Karring,et al.  Healing following implantation of periodontitis affected roots into bone tissue. , 1980, Journal of clinical periodontology.

[30]  Savita Khanna,et al.  Dermal wound healing is subject to redox control. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[31]  L. Toy Matrix metalloproteinases: their function in tissue repair. , 2005, Journal of wound care.

[32]  S. Ghosh,et al.  Role of nuclear factor-kappaB in the immune system and bone. , 2005, Immunological reviews.

[33]  S. Bressler,et al.  The regulated synthesis of versican, decorin, and biglycan: extracellular matrix proteoglycans that influence cellular phenotype. , 2004, Critical reviews in eukaryotic gene expression.

[34]  H. Moses,et al.  Regulation of differentiation by TGF-beta. , 1996, Current opinion in genetics & development.

[35]  B. McAllister,et al.  Signal transduction mechanisms in mesenchymal cells. , 1994, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.