RESEARCH PAPER
The association of bone turnover markers with pro- and anti-inflammatory adipokines in patients with gestational diabetes
 
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1
Department of Endocrinology, Diabetology and Internal Medicine, Medical University, Bialystok, Poland
 
2
Department of Gynecology, Medical University, Bialystok, Poland
 
 
Ann Agric Environ Med. 2015;22(2):307-312
 
KEYWORDS
ABSTRACT
Objective:
The aim of the study was to assess differences in circulating osteocalcin (OC) and osteoprotegerin (OPG), as well as in their expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT).

Material and Methods:
Serum levels of OC, OPG and soluble nuclear factor-kB ligand (sRANKL) were measured in 49 women with GDM and 30 subjects with NGT between weeks 24–32 of gestation, and three months after childbirth. OC and OPG mRNA expression was measured in 23 patients with GDM and 23 women with NGT at term, using quantitative real-time RT-PCR.

Results:
The patients with GDM had decreased OC mRNA expression in SAT (p=0.015), lower adiponectin mRNA expression in VAT (p=0.039), and a lower circulating adiponectin level (p=0.04). Multiple regression analysis revealed that serum adiponectin was significantly associated with OC mRNA expression in SAT (b=0.49, p=0.03). Three months postpartum, the OPG/sRANKL ratio was markedly higher in the subjects with prior GDM (p=0.03) and correlated positively with HbA1c (R=0.33; p=0.04), fasting insulin (R=0.35; p=0.03) and HOMA-IR (R=0.34; p=0.04).

Conclusions:
In the patients with GDM decreased OC mRNA expression in SAT might be associated with a reduced stimulatory effect on adiponectin expression in adipose tissue. On the other hand, higher OPG/sRANKL ratio suggests a better protection against bone loss in the subjects with prior GDM.

ACKNOWLEDGEMENTS
The study was supported by the State Committee for Scientific Research (Grant No. N N407 141937).
 
REFERENCES (25)
1.
Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care 2007; 30(Suppl. 2): 112–119.
 
2.
Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA. 2008; 105(13): 5266–5270.
 
3.
Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 2010; 142(2): 296–308.
 
4.
Collin-Osdoby P, Rothe L, Anderson F, Nelson M, Maloney W, Osdoby P. Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis. J Biol Chem. 2001; 276(23): 20659–20672.
 
5.
Winhofer Y, Handisurya A, Tura A, Bittighofer C, Klein K, Schneider B, et al. Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care 2010; 33(1): 139–143.
 
6.
Foresta C, Strapazzon G, De Toni L, Gianesello L, Calcagno A, Pilon C, et al. Evidence for osteocalcin production by adipose tissue and its role in human metabolism. J Clin Endocrinol Metab. 2010; 95(7): 3502–3506.
 
7.
An JJ, Han DH, Kim DM, Kim SH, Rhee Y, Lee EJ, et al. Expression and regulation of osteoprotegerin in adipose tissue. Yonsei Med J. 2007; 48(5): 765–772.
 
8.
Skopková M, Penesová A, Sell H, Rádiková Z, Vlcek M, Imrich R, et al. Protein array reveals differentially expressed proteins in subcutaneous adipose tissue in obesity. Obesity (Silver Spring.) 2007; 15(10): 2396–2406.
 
9.
Fain JN, Buehrer B, Bahouth SW, Tichansky DS, Madan AK. Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue. Metabolism 2008; 57(7): 1005–1015.
 
10.
Witasp A, Carrero JJ, Hammarqvist F, Qureshi AR, Heimbürger O, Schalling M, et al. Expression of osteoprotegerin in human fat tissue; implications for chronic kidney disease. Eur J Clin Invest. 2011; 41(5): 498–506.
 
11.
Plaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002; 30(9): e36.
 
12.
Flemming GM, Petzold S, Meigen C, Körner A, Kiess W, Kratzsch J. Is circulating osteocalcin related to adipokines and overweight/obesity in children and adolescents? Exp Clin Endocrinol Diabetes. 2012; 120(7): 383–387.
 
13.
Fisher A, Srikusalanukul W, Davis M, Smith P. Interactions between serum adipokines and osteocalcin in older patients with hip fracture. Int J Endocrinol. 2012. doi: 10.1155/2012/684323.
 
14.
Kalra PS, Dube MG, Iwaniec UT. Leptin increases osteoblast-specific osteocalcin release through a hypothalamic relay. Peptides 2009; 30(5): 967–973.
 
15.
Hinoi E, Gao N, Jung DY, Yadav V, Yoshizawa T, Myers MG Jr, et al. The sympathetic tone mediates leptin’s inhibition of insulin secretion by modulating osteocalcin bioactivity. J Cell Biol. 2008; 183(7): 1235–1242.
 
16.
Harsløf T, Husted LB, Carstens M, Stenkjaer L, Sørensen L, Pedersen SB, Langdahl BL. The expression and regulation of bone-acting cytokines in human peripheral adipose tissue in organ culture. Horm Metab Res. 2011; 43(7): 477–482.
 
17.
Xie H, Xie PL, Wu XP, Chen SM, Zhou HD, Yuan LQ, et al. Omentin-1 attenuates arterial calcification and bone loss in osteoprotegerin-deficient mice by inhibition of RANKL expression. Cardiovasc Res. 2011; 92(2): 296–306.
 
18.
Akesson A, Vahter M, Berglund M, Eklöf T, Bremme K, Bjellerup P. Bone turnover from early pregnancy to postweaning. Acta Obstet Gynecol Scand. 2004; 83(11): 1049–1055.
 
19.
Dorota DK, Bogdan KG, Mieczyslaw G, Bozena LG, Jan O. The concentrations of markers of bone turnover in normal pregnancy and preeclampsia. Hypertens Pregnancy 2012; 31(1): 166–176.
 
20.
Naylor KE, Rogers A, Fraser RB, Hall V, Eastell R, Blumsohn A. Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation. J Clin Endocrinol Metab. 2003; 88(11): 5361–5365.
 
21.
Bord S, Ireland DC, Beavan SR, Compston JE. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 2003; 32(2): 136–141.
 
22.
Madarász E, Tamás G, Tabák AG, Speer G, Lakatos P, Kerényi Z. Osteoprotegerin levels in women with prior gestational diabetes mellitus. Diabetes Care 2009; 32(1): e5.
 
23.
Akinci B, Demir T, Celtik A, Baris M, Yener S, Ozcan MA, Yuksel F, Secil M, Yesil S. Serum osteoprotegerin is associated with carotid intima media thickness in women with previous gestational diabetes. Diabetes Res Clin Pract. 2008; 82(2): 172–178.
 
24.
Akinci B, Celtik A, Yuksel F, Genc S, Yener S, Secil M, Ozcan MA, Yesil S. Increased osteoprotegerin levels in women with previous gestational diabetes developing metabolic syndrome. Diabetes Res Clin Pract. 2011; 91(1): 26–31.
 
25.
Augoulea A, Vrachnis N, Lambrinoudaki I, Dafopoulos K, Iliodromiti Z, Daniilidis A, et al. Osteoprotegerin as a marker of atherosclerosis in diabetic patients. Int J Endocrinol. 2013. doi: 10.1155/2013/182060.
 
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