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

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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