Evaluation of beta‐2 microglobulin and alpha‐2 macroglobulin levels in patients with different periodontal diseases

Ertuğrul, Abdullah Seçkin; Sahin, Hacer; Dikilitaş, Ahu; Alpaslan, Nuh; Bozoğlan, Alihan

doi:10.1111/adj.12022

Cited by 16 publications

(17 citation statements)

References 31 publications

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“…While potential pleiotropic effects of A2ML1 remain to be fully resolved, our data showed that A2ML1 variants are not associated with oral disease. Previously A2M protein was found to be higher in gingival crevicular fluid of patients with gingivitis and chronic periodontitis, but whether A2M plays a role in pathogenesis or is merely a marker for inflammation is unknown (Ertugrul, Sahin, Dikilitas, Alpaslan, & Bozoglan, ). We first hypothesized that the structural similarity between A2M and A2ML1 might translate to an increased risk for dental disease conferred by A2ML1 variants.…”

Section: Discussionmentioning

confidence: 99%

A2ML1and otitis media: novel variants, differential expression, and relevant pathways

Larson¹,

Magno²,

Steritz³

et al. 2019

Human Mutation

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A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media. K E Y W O R D S A2ML1, alpha-2-macroglobulin-like-1, exome sequencing, otitis media, RNA-sequencing

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Section: Discussionmentioning

confidence: 99%

A2ML1and otitis media: novel variants, differential expression, and relevant pathways

Larson¹,

Magno²,

Steritz³

et al. 2019

Human Mutation

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“…Eighteen papers were reviewed. Case definitions and methodologic approaches differed substantially . Of note, Teles et.…”

Section: Literature Reviewmentioning

confidence: 99%

“…Case definitions and methodologic approaches differed substantially. 27,[75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91] Of note, Teles et. al.…”

Section: Generalized Aggressive Periodontitismentioning

confidence: 99%

Classification and diagnosis of aggressive periodontitis

Fine

Patil

Loos

2018

J Clinic Periodontology

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Conflicting data resulted for several reasons; 1) the classification was too broad, 2) the disease (AgP) was not studied from its inception, at differing time points (temporal), and at different locations (topographic). New technologic advances coupled with a more delimiting definition of disease will allow for genetic, host and microbial factor analyses in an unbiased manner. As such we predict that progress can be made in identifying a robust group of genetic, host, and microbial risk-markers associated with periodontal disease that can improve diagnostic capability in disease associated with juveniles, adolescents, and post-adolescent individuals.

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“…A2M is a protease inhibitor known to exert a key role in the immune system although its mechanisms are not completely understood. It is associated with tissue destruction in periodontitis and is suggested to inhibit inflammation and to suppress proliferation of microorganisms[63]. A2M is also implicated in cartilage degradation, it is known to interact with the osteogenic growth peptide, osteoprotegerin (OPG), and suggested to inhibit BMP-1[64].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Peri-Implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway In Vivo

et al. 2014

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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.

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Evaluation of beta‐2 microglobulin and alpha‐2 macroglobulin levels in patients with different periodontal diseases

Cited by 16 publications

References 31 publications

A2ML1and otitis media: novel variants, differential expression, and relevant pathways

A2ML1and otitis media: novel variants, differential expression, and relevant pathways

Classification and diagnosis of aggressive periodontitis

Gene Expression Profiling of Peri-Implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway In Vivo

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