Expression of osteoprotegerin in human fat tissue; implications for chronic kidney disease

Abstract

Premature vascular calcification (or rather ossification) significantly contributes to morbidity and mortality in patients with chronic kidney disease stage 5 (CKD-5) and is linked to dysregulation of bone remodelling proteins. Recent evidence of a cross-talk between bone and fat tissue urged us to investigate whether the calcification/ossification-associated factors osteoprotegerin (OPG) and alpha-2-HS-glycoprotein (AHSG) are expressed in human uremic subcutaneous adipose tissue (SAT) and if the expression differs from nonuremic SAT. Abdominal SAT biopsies were obtained from 38 patients with CKD-5 [16 women, 58 (22-73) years old] during the surgical insertion of a peritoneal dialysis catheter and 20 controls [11 females, 56 (40-77) years old] undergoing elective hernia repair or laparoscopic cholecystectomy. Real-time polymerase chain reaction (PCR) quantifications were performed followed by immunohistochemical staining and serum protein concentration measurements. Relative mRNA expression and protein concentrations were evaluated together with clinical parameters. An additional 59 patients with CKD-5 were included for replication of statistical analyses. OPG but not AHSG mRNAs were detected in SAT, which were also positively immunolabelled for OPG. OPG mRNA levels were reduced (P = ·0001) and serum OPG concentrations were elevated (P < 0·0001), both about twofold, in patients compared to controls. Circulating OPG increased in proportion to BMI. Human SAT expresses OPG but not AHSG, and OPG expression is reduced in patients with CKD-5 when compared to controls, despite increased circulating protein levels.