title: Endostatin inhibits VEGF-A induced osteoclastic bone resorption in vitro.
abstract: BACKGROUND
  Endostatin is a C-terminal fragment of collagen XVIII which is a component of basement membranes with the structural properties of both collagens and proteoglycans. Endostatin has a major role in angiogenesis which is intimately associated with bone development and remodeling. Signaling between the endothelial cells and the bone cells, for example, may have a role in recruitment of osteoclastic precursor cells. Our study aims at exploring a possibility that endostatin, either as a part of basement membrane or as a soluble molecule, may control osteoclastogenesis and osteoclastic bone resorption in vitro.
  
  
  METHODS
  Rat pit formation assay was employed in order to examine the effect of endostatin alone or in combination with vascular endothelial growth factor-A (VEGF-A) on bone resorption in vitro. Effect of these agents on osteoclast differentiation in vitro was also tested. Osteoclastogenesis and the number of osteoclasts were followed by tartrate resistant acid phosphatase (TRACP) staining and resorption was evaluated by measuring the area of excavated pits.
  
  
  RESULTS
  Endostatin inhibited the VEGF-A stimulated osteoclastic bone resorption, whereas endostatin alone had no effect on the basal resorption level in the absence of VEGF-A. In addition, endostatin could inhibit osteoclast differentiation in vitro independent of VEGF-A.
  
  
  CONCLUSIONS
  Our in vitro data indicate that collagen XVIII/endostatin can suppress VEGF-A induced osteoclastic bone resorption to the basal level. Osteoclastogenesis is also inhibited by endostatin. The regulatory effect of endostatin, however, is not critical since endostatin alone does not modify the basal bone resorption.
authors.affiliation: Dept. of Anatomy and Cell Biology, PO Box 5000, FIN-90014 University of Oulu, Finland. annina.sipola@oulu.fi
authors.forename: Annina
authors.initials: A
authors.lastname: Sipola
authors.forename: Katri
authors.initials: K
authors.lastname: Nelo
authors.forename: Timo
authors.initials: T
authors.lastname: Hautala
authors.forename: Joanna
authors.initials: J
authors.lastname: Ilvesaro
authors.forename: Juha
authors.initials: J
authors.lastname: Tuukkanen
mesh_terms: D000135:Acid Phosphatase; D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D043170:Collagen Type XVIII / Q000494:pharmacology; D043169:Endostatins / Q000502:physiology*; D007527:Isoenzymes; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D043170:Collagen Type XVIII; D043169:Endostatins; D007527:Isoenzymes; D042461:Vascular Endothelial Growth Factor A; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase