title: The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy.
abstract: OBJECTIVE
  To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA).
  
  
  METHODS
  Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis.
  
  
  RESULTS
  MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP.
  
  
  CONCLUSIONS
  Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA.
authors.affiliation: School of Veterinary and Biomedical Sciences, Murdoch University, Perth, WA 6105, Australia. mcake@murdoch.edu.au
authors.forename: Martin A
authors.initials: MA
authors.lastname: Cake
authors.forename: Richard A
authors.initials: RA
authors.lastname: Read
authors.forename: Richard C
authors.initials: RC
authors.lastname: Appleyard
authors.forename: Su-Yang
authors.initials: SY
authors.lastname: Hwa
authors.forename: Peter
authors.initials: P
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D008592:Menisci, Tibial / Q000601:surgery; D023421:Models, Animal; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D020370:Osteoarthritis, Knee / Q000473:pathology*; D012756:Sheep
chemical_list: D020030:Nitric Oxide Donors; D005996:Nitroglycerin