Regulation of osteoclast differentiation and skeletal maintenance by histone deacetylases

Bora Faulkner, Kristina Astleford, Kim Mansky

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.

Original languageEnglish (US)
Article number1355
JournalMolecules
Volume24
Issue number7
DOIs
StatePublished - Jan 1 2019

Fingerprint

Histone Deacetylases
Osteoclasts
bones
gene expression
maintenance
Bone
Gene expression
Maintenance
Gene Expression
Co-Repressor Proteins
Bone and Bones
Histone Code
Bone Matrix
osteoporosis
Bone Resorption
Osteogenesis
phenotype
Osteoporosis
Cues
Extracellular Matrix

Keywords

  • Acetylation
  • Differentiation and resorption
  • Gene
  • HDAC
  • Osteoclasts
  • Transcription

Cite this

Regulation of osteoclast differentiation and skeletal maintenance by histone deacetylases. / Faulkner, Bora; Astleford, Kristina; Mansky, Kim.

In: Molecules, Vol. 24, No. 7, 1355, 01.01.2019.

Research output: Contribution to journalReview article

@article{a37afec31d75436f8bdc2048545faea2,
title = "Regulation of osteoclast differentiation and skeletal maintenance by histone deacetylases",
abstract = "Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.",
keywords = "Acetylation, Differentiation and resorption, Gene, HDAC, Osteoclasts, Transcription",
author = "Bora Faulkner and Kristina Astleford and Kim Mansky",
year = "2019",
month = "1",
day = "1",
doi = "10.3390/molecules24071355",
language = "English (US)",
volume = "24",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",

}

TY - JOUR

T1 - Regulation of osteoclast differentiation and skeletal maintenance by histone deacetylases

AU - Faulkner, Bora

AU - Astleford, Kristina

AU - Mansky, Kim

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.

AB - Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.

KW - Acetylation

KW - Differentiation and resorption

KW - Gene

KW - HDAC

KW - Osteoclasts

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=85064071408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064071408&partnerID=8YFLogxK

U2 - 10.3390/molecules24071355

DO - 10.3390/molecules24071355

M3 - Review article

VL - 24

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 7

M1 - 1355

ER -