title: Cathepsin K expression and activity in canine osteosarcoma.
abstract: BACKGROUND
  Cathepsin K (CatK) is a lysosomal protease with collagenolytic activity, and its secretion by osteoclasts is responsible for degrading organic bone matrix. People with pathologic bone resorption have higher circulating CatK concentrations.
  
  
  OBJECTIVE
  Canine osteosarcoma (OS) cells will possess CatK, and its secretion will be cytokine inducible. Circulating CatK concentrations will be increased in dogs with OS, and will be a surrogate marker of bone resorption.
  
  
  METHODS
  Fifty-one dogs with appendicular OS and 18 age- and weight-matched healthy control dogs.
  
  
  METHODS
  In a prospective study, expressions of CatK mRNA and protein were investigated in OS cells. The inducible secretion and proteolytic activity of CatK from OS cells was assessed in vitro. Serum CatK concentrations were quantified in normal dogs and dogs with OS and its utility as a bone resorption marker was evaluated in dogs with OS treated with palliative radiation and antiresorptive agents.
  
  
  RESULTS
  Canine OS cells contain preformed CatK within cytoplasmic vesicles. In OS cells, TGFβ1 induced the secretion of CatK, which degraded bone-derived type I collagen in vitro. CatK concentrations were higher in dogs with OS than healthy dogs (11.3 ± 5.2 pmol/L versus 8.1 ± 5.0 pmol/L, P = .03). In a subset of dogs with OS, pretreatment CatK concentrations gradually decreased after palliative radiation and antiresorptive treatment, from 9.3 ± 3.2 pmol/L to 5.0 ± 3.1 pmol/L, P = .03.
  
  
  CONCLUSIONS
  Canine OS is associated with pathologic bone resorption, and CatK inhibitors might aid in the management of canine OS-related malignant osteolysis.
authors.affiliation: Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Schmit
authors.forename: H C
authors.initials: HC
authors.lastname: Pondenis
authors.forename: A M
authors.initials: AM
authors.lastname: Barger
authors.forename: L B
authors.initials: LB
authors.lastname: Borst
authors.forename: L D
authors.initials: LD
authors.lastname: Garrett
authors.forename: J M
authors.initials: JM
authors.lastname: Wypij
authors.forename: Z L
authors.initials: ZL
authors.lastname: Neumann
authors.forename: T M
authors.initials: TM
authors.lastname: Fan
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000201:enzymology / Q000662:veterinary*; D056657:Cathepsin K / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D004283:Dog Diseases / Q000201:enzymology*; D004285:Dogs; D007150:Immunohistochemistry / Q000662:veterinary; D012516:Osteosarcoma / Q000201:enzymology / Q000662:veterinary*; D011446:Prospective Studies; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D053773:Transforming Growth Factor beta1; D012313:RNA; D056657:Cathepsin K