Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation

Skeletogenesis, remodeling, and maintenance in adult tissues are regulated by sequential activation of genes coding for specific transcription factors. The conserved Homeobox genes (<i>HOX</i>, in humans) are involved in several skeletal pathologies. Osteoarthritis (OA) is characterized...

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Main Authors: Arkaitz Mucientes, Eva Herranz, Enrique Moro, Cristina Lajas, Gloria Candelas, Benjamín Fernández-Gutiérrez, José Ramón Lamas
Format: Article
Language:English
Published: MDPI AG 2018-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/7/12/244
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author Arkaitz Mucientes
Eva Herranz
Enrique Moro
Cristina Lajas
Gloria Candelas
Benjamín Fernández-Gutiérrez
José Ramón Lamas
author_facet Arkaitz Mucientes
Eva Herranz
Enrique Moro
Cristina Lajas
Gloria Candelas
Benjamín Fernández-Gutiérrez
José Ramón Lamas
author_sort Arkaitz Mucientes
collection DOAJ
description Skeletogenesis, remodeling, and maintenance in adult tissues are regulated by sequential activation of genes coding for specific transcription factors. The conserved Homeobox genes (<i>HOX</i>, in humans) are involved in several skeletal pathologies. Osteoarthritis (OA) is characterized by homeostatic alterations of cartilage and bone synthesis, resulting in cartilage destruction and increased bone formation. We postulate that alterations in <i>HOX</i> expression in Mesenchymal Stem cells (MSCs) are likely one of the causes explaining the homeostatic alterations in OA and that this altered expression could be the result of epigenetic regulation. The expression of <i>HOX</i> genes in osteoarthritic-derived MSCs was screened using PCR arrays. Epigenetic regulation of <i>HOX</i> was analyzed measuring the degree of DNA methylation in their promoters. We demonstrate the downregulated expression of <i>HOXA9</i> and <i>HOXC8</i> in OA-MSCs. However, their expression does not correlate with promoter methylation status, suggesting that other epigenetic mechanisms could be implicated in the regulation of <i>HOX</i> expression. Studies on the role of these genes under active differentiation conditions need to be addressed for a better knowledge of the mechanisms regulating the expression of <i>HOX</i>, to allow a better understanding of OA pathology and to define possible biomarkers for therapeutic treatment.
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spelling doaj.art-219d0440ea2a41ddaa390f07d0c455ad2023-08-02T05:25:28ZengMDPI AGCells2073-44092018-12-0171224410.3390/cells7120244cells7120244Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter MethylationArkaitz Mucientes0Eva Herranz1Enrique Moro2Cristina Lajas3Gloria Candelas4Benjamín Fernández-Gutiérrez5José Ramón Lamas6Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Traumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 28040 Madrid, SpainSkeletogenesis, remodeling, and maintenance in adult tissues are regulated by sequential activation of genes coding for specific transcription factors. The conserved Homeobox genes (<i>HOX</i>, in humans) are involved in several skeletal pathologies. Osteoarthritis (OA) is characterized by homeostatic alterations of cartilage and bone synthesis, resulting in cartilage destruction and increased bone formation. We postulate that alterations in <i>HOX</i> expression in Mesenchymal Stem cells (MSCs) are likely one of the causes explaining the homeostatic alterations in OA and that this altered expression could be the result of epigenetic regulation. The expression of <i>HOX</i> genes in osteoarthritic-derived MSCs was screened using PCR arrays. Epigenetic regulation of <i>HOX</i> was analyzed measuring the degree of DNA methylation in their promoters. We demonstrate the downregulated expression of <i>HOXA9</i> and <i>HOXC8</i> in OA-MSCs. However, their expression does not correlate with promoter methylation status, suggesting that other epigenetic mechanisms could be implicated in the regulation of <i>HOX</i> expression. Studies on the role of these genes under active differentiation conditions need to be addressed for a better knowledge of the mechanisms regulating the expression of <i>HOX</i>, to allow a better understanding of OA pathology and to define possible biomarkers for therapeutic treatment.https://www.mdpi.com/2073-4409/7/12/244osteoarthritis (OA)cartilagebone<i>HOX</i>homeoboxmesenchymal stem cellsepigeneticsmethylation
spellingShingle Arkaitz Mucientes
Eva Herranz
Enrique Moro
Cristina Lajas
Gloria Candelas
Benjamín Fernández-Gutiérrez
José Ramón Lamas
Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation
Cells
osteoarthritis (OA)
cartilage
bone
<i>HOX</i>
homeobox
mesenchymal stem cells
epigenetics
methylation
title Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation
title_full Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation
title_fullStr Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation
title_full_unstemmed Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation
title_short Differential Expression of <i>HOX</i> Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation
title_sort differential expression of i hox i genes in mesenchymal stem cells from osteoarthritic patients is independent of their promoter methylation
topic osteoarthritis (OA)
cartilage
bone
<i>HOX</i>
homeobox
mesenchymal stem cells
epigenetics
methylation
url https://www.mdpi.com/2073-4409/7/12/244
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AT enriquemoro differentialexpressionofihoxigenesinmesenchymalstemcellsfromosteoarthriticpatientsisindependentoftheirpromotermethylation
AT cristinalajas differentialexpressionofihoxigenesinmesenchymalstemcellsfromosteoarthriticpatientsisindependentoftheirpromotermethylation
AT gloriacandelas differentialexpressionofihoxigenesinmesenchymalstemcellsfromosteoarthriticpatientsisindependentoftheirpromotermethylation
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