title: Pericyst may be a new pharmacological and therapeutic target for hydatid disease.
abstract: BACKGROUND
  Most hydatid cysts with calcified walls are biologically and clinically silent and inactive. Transforming growth factor-beta 1 (TGF-β1) plays a critical role in the calcification process of cells. The aim of this study was to assess the effect of modulating TGF-β1 signaling on the calcification of hydatid cysts.
  
  
  METHODS
  Pericyst cells isolated from hepatic hydatid cysts were cultured with osteogenic media. These cells were assessed for alkaline phosphatase activity and mineralization capacity using Alizarin Red staining. Cells were also treated with recombinant human TGF-β1 and TGF-β inhibitor, and the expression profiles of osteoblast markers (RUNX2, osterix, and osteocalcin) were analyzed using Western blotting. The effects of inhibiting TGF-β1 signaling on calcification of pericyst walls were assessed using different doses of TGF-β inhibitor for 7 weeks in a preclinical disease model of liver cystic echinococcosis.
  
  
  RESULTS
  Cells within the pericyst displayed high levels of alkaline phosphatase activity and mineralized nodule formation, as induced by osteogenic media. These activities, as well as expression profiles of osteoblast markers (RUNX2, osterix, and osteocalcin) could be inhibited by addition of recombinant human TGF-β1 (rhTGF-β1) and enhanced by TGF-β inhibitor. In the animal model of cystic echinococcosis, inhibition of TGF-β1 signaling increased calcification of the pericyst wall, which was associated with decreased cyst load index and lower viability of protoscoleces.
  
  
  CONCLUSIONS
  Cells within the pericysts adopt an osteoblast-like phenotype and have osteogenic potential. Inhibition of TGF-β1 signaling increases hydatid cyst calcification. Pharmacological modulation of calcification in pericysts may be a new therapeutic target in the treatment of hydatid disease.
authors: Department of Hepatobiliary Surgery, School of Medicine, Shihezi University, Shihezi, Xinjiang 832000, China.
authors: Xiang-Wei
authors: XW
authors: Wu
authors: Xue-Ling
authors: XL
authors: Chen
authors: Shi-Jie
authors: SJ
authors: Zhang
authors: Xi
authors: X
authors: Zhang
authors: Hong
authors: H
authors: Sun
authors: Xin-Yu
authors: XY
authors: Peng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D004443:Echinococcosis / Q000378:metabolism* / Q000473:pathology; D048209:Echinococcus granulosus / Q000472:pathogenicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D050657:Core Binding Factor alpha Subunits; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin