Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark.
Horm Metab Res. 2011 Jun;43(7):477-82. doi: 10.1055/s-0031-1277156. Epub 2011 May 10.
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.
骨与脂肪之间的体液相互作用是一个日益受到关注的领域。我们研究了骨作用细胞因子的表达和调节，包括骨形态发生蛋白 2（BMP2）、结缔组织生长因子（CTGF）、护骨素（OPG）和转化生长因子β（TGFB1）。从健康的瘦人身上抽吸皮下脂肪组织。将组织样本与白细胞介素 1-β（IL1-β）、肿瘤坏死因子-α（TNF-α）、皮质醇、曲格列酮、IL1-β+曲格列酮或载体孵育。使用 qPCR 分析脂肪组织中的基因表达，使用 ELISA 分析孵育介质中的蛋白水平。皮质醇使 OPG 的表达和分泌分别减少了 40.8%和 43.1%，曲格列酮使 OPG 的表达减少了 67.5%（p<0.05）。促炎细胞因子 IL1-β 和 TNF-α 分别使 CTGF 的表达增加了 65.1%和 101.3%（p<0.05），并使 OPG 的表达和分泌增加了 62.3-165.8%（p<0.05）。这种白细胞介素 1-β 介导的 CTGF 和 OPG 表达和分泌的增加被曲格列酮改善。曲格列酮和相关药物已知对骨骼有不良影响。我们认为，这可能是通过改变脂肪组织中细胞因子的产生来介导的。此外，肥胖个体的脂肪组织存在低度炎症，并且比瘦个体具有更高的骨矿物质密度。我们认为，这种炎症可能会增加 OPG 和 CTGF 的表达和分泌，从而增加 BMD。总之，骨作用细胞因子在脂肪组织中产生，并可能通过内分泌机制影响骨骼。
