title: Lanthanum carbonate prevents accelerated medial calcification in uremic rats: role of osteoclast-like activity.
abstract: BACKGROUND
  Arterial medial calcification (AMC) is frequent prevalence in patients with end stage renal disease. Evidence about hyperphosphatemia induced anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare. Lanthanum carbonate as an orally administered phosphate-binding agent to reduce phosphate load and ameliorate AMC, but direct evidence is missing.
  
  
  METHODS
  Detailed time-course studies were conducted of Sprague-Dawley rats fed with adenine and high phosphate diet to imitate the onset and progression of AMC of uremia. Calcification in great arteries was evaluated by VonKossa's and Masson's trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL, Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT-PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit.
  
  
  RESULTS
  Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter group diminished significantly (2.92 ± 0.73 mmol/L vs CRF Group 3.48 ± 0.69, p < 0.01) at week 10. The rats that did not receive 2%La treatment had extensive von kossa staining for medial calcification in CRF group. In contrast, the rats in 2%La group just exhibit mild medial calcification. Inhibitory effect on progression of AMC was reflected by down regulated osteogenic genes and altered osteoclast-like genes. RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF group, p <0.01), whereas marginal difference in serum among the three groups. In contrast to the robust expression of cathepsinK in calcified area, TRAP expression was not found.
  
  
  CONCLUSIONS
  Abnormal phosphate homeostasis, induction of osteogenic conversion and osteoclast suppression were contributed to the current mechanisms of uremia associated arterial medial calcification based on our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the decreased phosphate retention and cross-talk between osteoblast and osteoclast-like cell, both of which can be the therapeutic target for uremia associated with AMC.
authors: Yu
authors: Y
authors: Che
authors: Chen
authors: C
authors: Bing
authors: Javed
authors: J
authors: Akhtar
authors: Zhao
authors: Z
authors: Tingting
authors: Yu
authors: Y
authors: Kezhou
authors: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Shandong 250021, P, R, China. wangrongsdu@163.com.
authors: Wang
authors: W
authors: Rong
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics; D000818:Animals; D002114:Calcinosis / Q000517:prevention & control*; D056657:Cathepsin K / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D054559:Hyperphosphatemia / Q000150:complications; D007527:Isoenzymes / Q000235:genetics; D007811:Lanthanum / Q000494:pharmacology*; D015675:Osteocalcin / Q000235:genetics; D010010:Osteoclasts / Q000473:pathology*; D053245:RANK Ligand / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase; D014511:Uremia / Q000150:complications / Q000473:pathology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D007527:Isoenzymes; D053245:RANK Ligand; C493717:Runx2 protein, rat; D015675:Osteocalcin; C119467:lanthanum carbonate; D007811:Lanthanum; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K