Apoptotic Genes are Differentially Expressed in Aged Gingival Tissue

González, Octavio A.; Stromberg, Arnold J.; Huggins, Peter; González‐Martínez, Janis; Novak, M. John; Ebersole, Jeffrey L.

doi:10.1177/0022034511403744

Cited by 55 publications

(111 citation statements)

References 30 publications

(35 reference statements)

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“…These results suggested a differential pattern of macrophage infiltration/differentiation/maturation in aged healthy tissues that tended towards increased inflammatory and tissue destructive macrophages (M1), even in healthy aged tissues. Thus, as we have found previously exploring gene expression profiles for other pathways (Gonzalez, Stromberg, Huggins, Gonzalez-Martinez, Novak and Ebersole, 2011, Gonzalez, John Novak, Kirakodu, Stromberg, Shen, Orraca, Gonzalez-Martinez and Ebersole, 2013, Gonzalez, Novak, Kirakodu, Orraca, Chen, Stromberg, Gonzalez-Martinez and Ebersole, 2014, Ebersole, Kirakodu, Novak, Stromberg, Shen, Orraca, Gonzalez-Martinez, Burgos and Gonzalez, 2014), while apparently clinically healthy, the aged gingival tissues seem to be fundamentally altered in the local environmental milieu of cellular functions that may present an enhanced predisposition to a tissue destructive process when challenged with a more pathogenic microbial stimulus. Additionally, in periodontitis tissues, increases in gene expression reflecting an increase in total macrophage populations appeared to be primarily related to increases in M1 cells, reflecting a response more skewed towards tissue destructive inflammation than was observed even in the adult periodontitis tissues.…”

Section: Discussionsupporting

confidence: 54%

“…Total RNA was isolated from each gingival tissue using a standard procedure as we have described and tissue RNA samples submitted to the microarray core to assess RNA quality analyze the transcriptome using the GeneChip® Rhesus Macaque Genome Array (Affymetrix) (Meka, Bakthavatchalu, Sathishkumar, Lopez, Verma, Wallet, Bhattacharyya, Boyce, Handfield, Lamont, Baker, Ebersole and Kesavalu, Gonzalez, Stromberg, Huggins, Gonzalez-Martinez, Novak and Ebersole, 2011). Individual samples were used for gene expression analyses.…”

Section: Methodsmentioning

confidence: 99%

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Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues

González

Novak

Kirakodu

et al. 2015

Immunological Investigations

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SUMMARY Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1, M2) of these cells in inflammation, adaptive immune responses, and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3–23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent, and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7, TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.

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Section: Discussionsupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues

González

Novak

Kirakodu

et al. 2015

Immunological Investigations

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“…Defects in cell proliferation in aged dermal fibroblasts have been explained by the loss of epidermal growth factor (EGF) receptors, leading to a reduced response to this mitogen (Shiraha et al, 2000). Although we did not evaluate apoptotic events in our study, previous studies have identified a high expression of pro-apoptotic genes in aged gingival tissues (González et al, 2011). In addition, aging affects telomeric length, pluripotency, and the cell proliferation potential of mesenchymal stem cells (Guillot et al, 2007).…”

Section: Discussionmentioning

confidence: 92%

Defective Wound-healing in Aging Gingival Tissue

Cáceres

Oyarzún

2014

J Dent Res

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Aging may negatively affect gingival wound-healing. However, little is known about the mechanisms underlying this phenomenon. The present study examined the cellular responses associated with gingival wound-healing in aging. Primary cultures of human gingival fibroblasts were obtained from healthy young and aged donors for the analysis of cell proliferation, cell invasion, myofibroblastic differentiation, and collagen gel remodeling. Serum from young and old rats was used to stimulate cell migration. Gingival repair was evaluated in SpragueDawley rats of different ages. Data were analyzed by the Mann-Whitney and Kruskal-Wallis tests, with a p value of .05. Fibroblasts from aged donors showed a significant decrease in cell proliferation, migration, Rac activation, and collagen remodeling when compared with young fibroblasts. Serum from young rats induced higher cell migration when compared with serum from old rats. After TGF-beta1 stimulation, both young and old fibroblasts demonstrated increased levels of alpha-SMA. However, alpha-SMA was incorporated into actin stress fibers in young but not in old fibroblasts. After 7 days of repair, a significant delay in gingival wound-healing was observed in old rats. The present study suggests that cell migration, myofibroblastic differentiation, collagen gel remodeling, and proliferation are decreased in aged fibroblasts. In addition, altered cell migration in wound-healing may be attributable not only to cellular defects but also to changes in serum factors associated with the senescence process.

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“…These species demonstrate clinical, microbiological, and immunologic similarities to the disease in humans. Most recently we have developed a collaborative arrangement with the Caribbean Primate Research Center in Sabana Seca, PR to evaluate the ontogeny of the immune system in gingival tissues across the lifespan [Ebersole et al, 2008; Gonzalez et al, 2011; Gonzalez et al, 2013]. This cohort of animals was derived from a large, free-ranging colony of rhesus monkeys that was created in 1938 by seeding 400 Indian rhesus monkeys onto the isolated island of “Cayo Santiago” off the southeast coast of Puerto Rico.…”

Section: Introductionmentioning

confidence: 99%

Familial periodontal disease in the cayo santiago rhesus macaques

González

Orraca

Kensler

et al. 2015

American J Primatol

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Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally-occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5–31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all 4 quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease.

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Apoptotic Genes are Differentially Expressed in Aged Gingival Tissue

Cited by 55 publications

References 30 publications

Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues

Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues

Defective Wound-healing in Aging Gingival Tissue

Familial periodontal disease in the cayo santiago rhesus macaques

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