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Sirtuins as Markers of Bone Disease: A Focus on Osteoarthritis and Osteoporosis

  • Élie Abed
  • Pascal Reboul
  • Daniel Lajeunesse
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)

Abstract

Sirtuins are widely distributed class III NAD+-dependent histone deacetylases (HDAC) involved in epigenetic regulation. There are seven protein members of the sirtuins, SIRT1-7, each of which specific sites of action linked with the intracellular localization, and acting on selective target proteins. Sirtuins are involved in a number of processes ranging from cell cycle regulation, apoptosis/proliferation, DNA repair, tumor suppression, energy metabolism, mitochondrial homeostasis, metabolism, cellular senescence/aging, and inflammation. Sirtuins also play a key role on the recruitment and differentiation of mesenchymal stem cells and via this pathway play an important role in the maintenance and function of bone tissue. Hence, sirtuins are involved in bone pathologies such as osteoarthritis and osteoporosis and can serve as biomarkers for these pathologies.

Keywords

Sirtuins Osteoarthritis Osteoporosis Mesenchymal stem cells Wnt/β-catenin 

List of abbreviations

ADP

Adenosine diphosphate

AMPK

5’ Adenosine monophosphate-activated protein kinase

AP1

Activator protein-1 complex IkBα and NF-kB

BMI

Body mass index

BMP2

Bone morphogenetic protein-2

Cbfa1/Runx2

Core-binding factor alpha 1/ Runt-related transcription factor 2

cWnt

Canonical Wnt/β-catenin

DAN

Cysteine-knot protein abberative in neuroblastoma

DKK1

Dickkoft-1

EP300

E1A binding protein p300

FoxO

Forkhead box O

Fz

Frizzled

GSK3β

Glycogen synthase kinase 3 beta

H3K9

Histone 3 is deacetylated at lysine

HATs

Histone acetyl transferases

hBMSC

Human bone marrow stromal cellsMmp13 matrix metalloproteinase-13

HDAC

NAD + -dependent histone deacetylases

HGF

Hepatocyte growth factor

IL

Interleukin

JNK

c-Jun N-terminal kinase

Lef

Lymphoid enhancer-binding factor

LRP5/6

Low-density lipoprotein receptor-related protein 5/6

LXR

Liver X receptor

MSC

Mesenchymal stem cell

NAD

Nicotinamide adenine dinucleotide

NANOG

Transcription factor critically involved with self-renewal of undifferentiated embryonic stem cells

OA

Osteoarthritis

OCT4

Octamer-binding transcription factor 4

OP

Osteoporosis

OPG

Osteoprotegerin

PGC-1α

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PKC

Protein kinase C

PPARγ

Peroxisome proliferator-activated receptor γ

PTH

Parathyroid hormone

RANKL

Receptor activator of nuclear factor kappa-B ligand

Rho GTPase

Rho family of guanosine triphosphate hydrolase

sFRP

Secreted frizzled-related proteins

SIRT1

Sirtuin 1

SIRT6

Sirtuin 6

SOST

Sclerostin

SOX2

SRY (sex determining region Y)-box 2

T2D

Type 2 diabetes

TCF

T cell factor

TGF-β1

Transforming growth factor beta-1

TNF

Tumor necrosis factor

Wif1

Wnt inhibitory factor 1

Wnt

Wingless

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© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Centre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)MontréalCanada
  2. 2.Biopôle de l’Université de Lorraine – Campus biologie-santéUMR7365 CNRS Université de Lorraine, IMoPAVandœuvre-lès-Nancy cedexFrance
  3. 3.Département of médicineCentre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Université de MontréalMontréalCanada

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