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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Anna
A
Witasp
Juan J
JJ
Carrero
Folke
F
Hammarqvist
Abdul R
AR
Qureshi
Olof
O
Heimbürger
Martin
M
Schalling
Bengt
B
Lindholm
Louise
L
Nordfors
Peter
P
Stenvinkel
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D053244:Osteoprotegerin; D060749:alpha-2-HS-Glycoprotein