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Horm Metab Res 2011; 43(7): 477-482
DOI: 10.1055/s-0031-1277156
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

The Expression and Regulation of Bone-acting Cytokines in Human Peripheral Adipose Tissue in Organ Culture

T. Harsløf1 , L. B. Husted1 , M. Carstens1 , L. Stenkjær1 , L. Sørensen1 , S. B. Pedersen1 , B. L. Langdahl1
  • 1Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark
Further Information

Publication History

received 12.01.2011

accepted 04.04.2011

Publication Date:
10 May 2011 (online)

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Abstract

The humoral cross-talk between bone and fat is an area of increasing interest. We investigated the expression and regulation of the bone-acting cytokines; bone morphogenetic protein 2 (BMP2), connective tissue growth factor (CTGF), osteoprotegerin (OPG), and transforming growth factor beta (TGFB1). Subcutaneous adipose tissue was aspirated from lean, healthy women. Tissue samples were incubated with interleukin 1-β (IL1-β), tumor necrosis factor-α (TNF-α), cortisol, troglitazone, IL1-β + troglitazone, or vehicle. Gene expression in the adipose tissue was analyzed using qPCR and protein levels in the incubation media were analyzed using ELISA. OPG expression and secretion was diminished by 40.8% and 43.1% respectively, by cortisol, and OPG expression was diminished by 67.5% by troglitazone (p<0.05). The proinflammatory cytokines IL1-β and TNF-α significantly increased the expression of CTGF (p<0.05) by 65.1% and 101.3%, respectively, and the expression and secretion of OGP by 62.3–165.8% (p<0.05). This interleukin 1-β mediated increase in CTGF- and OPG expression and secretion was ameliorated by troglitazone. Troglitazone and related drugs are known to have adverse effects on bone. We suggest that this could be mediated via altered cytokine production in adipose tissue. Moreover, obese individuals have a low-grade inflammation in their adipose tissue and have higher bone mineral density than lean individuals. We suggest that this inflammation may increase the expression and secretion of OPG and CTGF and thereby increase BMD. In conclusion, bone acting cytokines are produced in the adipose tissue and may affect bone through endocrine mechanisms.

Key words

adipose tissue - thiazolidinediones - inflammation - real-time PCR - ELISA

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Correspondence

T. Harsløf

Department of Endocrinology

and Internal Medicine

Aarhus University Hospital

Tage-Hansens Gade 2

8000 Aarhus C

Denmark

Phone: +45/894/976 81

Fax: +45/894/976 84

Email: torbhars@rm.dk