Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis

Sadaf Ashraf, Paul I Mapp, David A Walsh

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

Abstract

OBJECTIVE: To determine the contributions of angiogenesis to inflammation, joint damage, and pain behavior in a rat meniscal transection model of osteoarthritis (OA).

METHODS: OA was induced in male Lewis rats (n=8 per group) by meniscal transection. Animals were orally dosed with dexamethasone (0.1 mg/kg/day), indomethacin (2 mg/kg/day), or the specific angiogenesis inhibitor PPI-2458 (5 mg/kg every other day). Controls consisted of naive and vehicle-treated rats. Synovial inflammation was measured as the macrophage fractional area (expressed as the percentage), thickness of the synovial lining, and joint swelling. Synovial angiogenesis was measured using the endothelial cell proliferation index and vascular density. Channels positive for vessels at the osteochondral junction were assessed (osteochondral angiogenesis). Medial tibial plateaus were assessed for chondropathy, osteophytosis, and channels crossing the osteochondral junction. Pain behavior was measured as weight-bearing asymmetry.

RESULTS: Dexamethasone and indomethacin each reduced pain behavior, synovial inflammation, and synovial angiogenesis 35 days after meniscal transection. Dexamethasone reduced, but indomethacin had no significant effect on, the total joint damage score. PPI-2458 treatment reduced synovial and osteochondral angiogenesis, synovial inflammation, joint damage, and pain behavior.

CONCLUSION: Our findings indicate that synovial inflammation and joint damage are closely associated with pain behavior in the meniscal transection model of OA. Inhibition of angiogenesis may reduce pain behavior both by reducing synovitis and by preventing structural change. Targeting angiogenesis could therefore prove useful in reducing pain and structural damage in OA.

Original languageEnglish
Pages (from-to)2700-2710
Number of pages11
JournalArthritis & Rheumatism
Volume63
Issue number9
DOIs
Publication statusPublished - 2 May 2011

Keywords

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal/pharmacology
  • Behavior, Animal/drug effects
  • Cartilage, Articular/drug effects
  • Dexamethasone/pharmacology
  • Glucocorticoids/pharmacology
  • Indomethacin/pharmacology
  • Inflammation/complications
  • Joints/drug effects
  • Male
  • Neovascularization, Pathologic/complications
  • Osteoarthritis/complications
  • Pain/complications
  • Pain Measurement
  • Rats
  • Rats, Inbred Lew
  • Weight-Bearing/physiology

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