title: Fibrous tissue of subchondral cystic lesions in horses produce local mediators and neutral metalloproteinases and cause bone resorption in vitro.
abstract: OBJECTIVE
  To define the release of nitric oxide (NO), prostaglandin E2 (PGE2), and the neutral metalloproteinases (NMPs) in horses with subchondral cystic lesions (SCL) and to study bone resorption triggered by conditioned media of fibrous tissue of SCL in vitro.
  
  
  METHODS
  Equine explant cultures of fibrous tissue of SCL, and synovial membrane and articular cartilage of normal horses and horses affected with moderate and severe osteoarthritis were performed. NO, PGE2, and NMP concentrations of media samples were measured, and osteoclast formation and activation was studied in vitro.
  
  
  METHODS
  Experiment 1: 32 horses with SCL (n = 8), normal joints (7), and joints with moderate (7) and severe (10) osteoarthritis (OA). Experiment 2: 22 horses with SCL (n = 3), normal joints (7), and chip fractures (12). Experiment 3: Conditioned media of fibrous tissue from 3 horses with SCL of the medial femoral condyle (n = 1), distal metacarpal bone (1), and tarsal bone (1).
  
  
  METHODS
  Determinations of local mediator concentrations were made with the Griess assay for NO and an enzyme immunoassay kit for PGE2 concentrations in biological fluids. Enzyme activities were assessed with radiolabeled substrates indicating collagenolytic, gelatinolytic, and caseinolytic activities. The resorption pit assay was used to assess osteoclast recruitment and activity.
  
  
  RESULTS
  Fibrous tissue of SCL produced NO, PGE2, and NMPs. Of all the variables measured, PGE2 concentrations were the highest in cystic tissue of SCL compared with synovial membrane and articular cartilage from normal joints and joints with chip fractures, indicating that this mediator may play an important role in pathological bone resorption associated with SCL. These findings were supported by the observation that conditioned media of SCL tissue were capable of recruiting osteoclasts and increasing their activity.
  
  
  CONCLUSIONS
  Fibrous tissue of SCL released NO, PGE2, and NMPs into the culture media. It is suspected that intralesional fibrous tissue may play an active role in the pathological process of bone resorption occurring in SCL in horses and may be partly responsible for the maintenance, slow healing rate, and expansion of these lesions.
  
  
  CONCLUSIONS
  Understanding the pathogenesis of SCL will help to establish successful therapy in horses affected with SCL.
authors.affiliation: Department of Veterinary Surgery, University of Zürich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: von Rechenberg
authors.forename: H
authors.initials: H
authors.lastname: Guenther
authors.forename: C W
authors.initials: CW
authors.lastname: McIlwraith
authors.forename: C
authors.initials: C
authors.lastname: Leutenegger
authors.forename: D D
authors.initials: DD
authors.lastname: Frisbie
authors.forename: M K
authors.initials: MK
authors.lastname: Akens
authors.forename: J A
authors.initials: JA
authors.lastname: Auer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001845:Bone Cysts / Q000503:physiopathology / Q000662:veterinary*; D001862:Bone Resorption / Q000201:enzymology / Q000378:metabolism / Q000662:veterinary*; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism; D046508:Culture Techniques; D015232:Dinoprostone / Q000378:metabolism*; D006734:Horse Diseases / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006736:Horses; D008666:Metalloendopeptidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010003:Osteoarthritis / Q000503:physiopathology / Q000662:veterinary; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D008666:Metalloendopeptidases; D015232:Dinoprostone