title: Involvement of parathyroid hormone-related protein in vascular calcification of chronic haemodialysis patients.
abstract: OBJECTIVE
  To investigate the role of parathyroid hormone-related protein (PTHrP) in vascular calcification of patients with chronic hemodialysis.
  
  
  METHODS
  The inferior epigastric arteries were obtained from 23 patients on chronic haemodialysis and 16 patients with renal carcinoma as control. Haematoxylin-eosin staining, elastic fibre staining, Alizarin Red calcium staining and immunohistochemical staining of PTHrP, bone morphogenetic protein-2 (BMP-2), Cbfa1/Runx2 were performed. Real-time polymerase chain reaction (PCR) was used to examine mRNA expressions of PTHrP, BMP-2 and Cbfa1/Runx2. Western blot and real-time PCR were used to detect the effects of PTHrP-siRNA and rh-PTHrP-1-34 on the expressions of PTHrP, BMP-2 and Cbfa1/Runx2 in human aortic smooth muscle cells (HASMC). Alkaline phosphatase (ALP) activities and intracellular calcium content in HASMCs were assessed after treatment with 10 mmol/L β-glycerol phosphoric acid for 48 h.
  
  
  RESULTS
  Vascular calcification was confirmed in 78.2% of patients on chronic haemodialysis, and the expressions of PTHrP, BMP-2 and Cbfa1 in the arteries were significantly upregulated. PTHrP-siRNA could downregulate the expression of PTHrP by 60%, BMP-2 by 25% and Cbfa1 by 25% at 24 h (P < 0.05). Exogenous rh-PTHrP-1-34 could upregulate the expressions of BMP-2 and Cbfa1 by 1.37-fold and 1.46-fold, respectively, at 24 h in a time-independent manner (P < 0.05), which were attenuated by PTHrP-siRNA. Moreover, it could promote intracellular calcium deposition and increase ALP activities, which were partially blocked by PTHrP-siRNA (P < 0.05).
  
  
  CONCLUSIONS
  Vascular calcification was common in patients with chronic haemodialysis, to which PTHrP might contribute by activating BMP-2/ Cbfa1 signalling pathway.
authors.affiliation: Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
authors.forename: Wenxing
authors.initials: W
authors.lastname: Fan
authors.forename: Rong
authors.initials: R
authors.lastname: Gou
authors.forename: Youqun
authors.initials: Y
authors.lastname: Huang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Qiu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Songmin
authors.initials: S
authors.lastname: Huang
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001011:Aorta / Q000378:metabolism; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D019074:Epigastric Arteries / Q000378:metabolism; D005260:Female; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D006435:Renal Dialysis / Q000009:adverse effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013194:Staining and Labeling; D014162:Transfection; D061205:Vascular Calcification / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D005994:Glycerophosphates; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D000469:Alkaline Phosphatase; D002118:Calcium; C031463:beta-glycerophosphoric acid