title: Effects of PTH [1-34] on synoviopathy in an experimental model of osteoarthritis preceded by osteoporosis.
abstract: OBJECTIVE
  Synoviopathy contributes to cartilage degradation in osteoarthritis (OA). Intermittent parathyroid hormone (PTH) [1-34] administration inhibits terminal differentiation of human chondrocytes and prevents cartilage damage. We aimed to determine whether PTH [1-34] could modify synovial changes in experimental OA preceded by osteoporosis (OP).
  
  
  METHODS
  Twenty osteoporosis (OP) rabbits underwent knee surgery to induce OA. They were administered either saline vehicle or PTH for 10 weeks. Ten healthy rabbits were used as controls. Following sacrifice, synovial changes were assessed by Krenn synovitis score, immunohistochemistry for macrophages (RAM-11), B and T lymphocytes, type I collagen, parathyroid hormone 1 receptor (PTH1R), and anti-proliferating cell nuclear antigen (PCNA). Synovial mRNA levels of Col1A1, IL-1β, cyclooxygenase 2 (COX-2), matrix-degrading metalloproteinases (MMP-9, MMP-13), and monocyte chemotactic protein-1 (MCP-1), as well as protein expression of PTH1R were also determined. Cartilage damage was analyzed by Mankin score.
  
  
  RESULTS
  OPOA + vehicle rabbits showed an increase in synovitis score vs controls (P = 0.003), mainly due to synovial hyperplasia and fibrosis, while PTH reduced these changes (P = 0.017). Mankin and Krenn scores were well correlated in all groups (r = 0.629, P = 0.012). Immunostaining for RAM-11 and B lymphocytes was increased (P ≤ 0.05), whereas PTH1R protein levels tended to be higher in OPOA + vehicle animals vs controls. PTH did not modify RAM-11 staining or PTH1R levels; however, it restored PTH1R localization to the vicinity of synovial vessels. PTH also decreased type I collagen, MCP-1, and MMP-13 expression (P < 0.05), as well as PCNA staining compared to vehicle-treated OPOA rabbits.
  
  
  CONCLUSIONS
  In our model of OA aggravated by previous OP, synoviopathy correlated well with cartilage damage. Intermittent PTH [1-34] administration ameliorated both hyperplasia and fibrosis.
authors.affiliation: Bone and Joint Research Unit, Rheumatology Service, IIS Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain. llugo@fjd.es
authors.forename: L
authors.initials: L
authors.lastname: Lugo
authors.forename: A
authors.initials: A
authors.lastname: Villalvilla
authors.forename: R
authors.initials: R
authors.lastname: Gómez
authors.forename: M
authors.initials: M
authors.lastname: Bellido
authors.forename: O
authors.initials: O
authors.lastname: Sánchez-Pernaute
authors.forename: R
authors.initials: R
authors.lastname: Largo
authors.forename: G
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.forename: J A
authors.initials: JA
authors.lastname: Roman-Blas
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D015153:Blotting, Western; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000150:complications* / Q000473:pathology; D010024:Osteoporosis / Q000150:complications* / Q000473:pathology; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D012313:RNA / Q000096:biosynthesis; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D010281:Parathyroid Hormone; D012313:RNA