
DO WE USE METHYLATION OF NFATC1 AND FOS GENES AS
A BIOMARKER FOR POSTMENOPAUSAL OSTEOPOROSIS? Kalkan R, Tosun O *Corresponding Author: Associate Professor Rasime Kalkan, Department of Medical Genetics, Faculty
of Medicine, Near East University, Near East Boulevard, Nicosia, Cyprus, 99138. Tel: +903-92-
223-6464. Fax: +903-92-223-6461. E-mail: rasime.kalkan@neu.edu.tr, kalkanr@yahoo.com page: 35
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INTRODUCTION
The nuclear factor of activated T-cell gene family
contains five members; which are NFATC1, NFATC2,
NFATC3, NFATC4 and NFATC5 [1]. This gene family is
regulated by the calcium signaling pathway [1], which
plays an important role during the regulation of the different
systems; for instance, immune system [2], skeletal
system and circulatory system [2-4]. NFATC1 regulates osteoclast-
specific genes for osteoclast differentiation, such
as TRAP, cathepsin K, calcitonin receptor and FOS [5-8].
The osteoclast differentiation pathway was under control
of RANKL [receptor activator of nuclear factor-κ B (NF-
κB) ligand], NF-κB and FOS signaling [9]. The RANK/
RANKL is an important pathway for bone remodeling [10],
which activates FOS and triggers NFATC1 expression [8].
The interaction between FOS and osteoclast differentiation
was observed in mice, and researchers showed osteoporosis
development in FOS knockout mice [5,11].
Due to the genetic and epigenetic factors, osteoporosis
has been reported as a multifactorial disease [12].
Several association studies had been done but the etiology
and molecular mechanism of the disease is not clearly explained.
During the menopause, the deficiency of estrogen
causes increased level of the follicle-stimulating hormone
(FSH) which accelerates bone loss [13]. Differential gene
expression of bone cells has been done to solve this complex
interaction [14,15]. Liu et al. [16] used circulating
monocytes for genome wide differential gene expression
analysis in osteoporotic and non osteoporotic postmenopausal
Caucasian females, and they identified differential
gene expression in circulating monocytes. In general studies
that analyzed the effect of estrogens, corticosteroids and
oxidative stress on osteoblast cells [15,17] showed the gene
expression profile or polymorphisms of different genes in
premenopausal and primary osteoporosis women [15,18]. To the best of our knowledge, there are no epigenetic
studies of NFATC1 and FOS genes in postmenopausal
women. In this study, we aim to analyze methylation status
of NFATC1 and FOS genes in post- and premenopausal
women and show their association with menopausal osteoporosis.
Based on the current literature, this is the first
epigenetic study on postmenopausal women that shows
postmenopausal osteoporosis and NFATC1 gene interaction.
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