The infrapatellar fat pad is affected by injury induced inflammation in the rabbit knee: use of dexamethasone to mitigate damage

Inflamm Res. 2016 Jun;65(6):459-70. doi: 10.1007/s00011-016-0928-z. Epub 2016 Feb 22.

Abstract

Objective and design: The health of the infrapatellar fat pad (IFP) has been linked to pain, joint inflammation, and the onset of post-traumatic osteoarthritis. Thus, early inflammation effects on the IFP could have long term sequelae on joint integrity. This study was designed to characterize the natural history of the IFP in a model of surgically induced knee injury and inflammation, and to test the efficacy of one intra-articular (IA) administration of dexamethasone (DEX) immediately following surgery.

Methods: An IA bone drill hole injury to the rabbit knee was conducted and immediately treated with DEX (n = 12). Early and late post-surgical time-points were investigated (48 h and 9 weeks) and the outcome measures were analysis of IFP histology, mRNA levels for relevant molecules, and protein levels for a subset of cytokines. Data were analyzed against a surgical control (injury without treatment; n = 12), a surgical sham (capsular incision only; n = 12), and normal control (n = 6).

Treatment: Single IA injection of DEX (0.5 mg/kg), administered at the completion of surgery.

Results: IFPs from injured joints exhibited significantly increased cellularity and early fibrosis at 48 h post surgery. While the histological inflammation from a capsular incision alone resolved, knee injured animals progressed to a significantly more fibrotic IFP by 9 weeks. DEX significantly lowered histological scores at 48 h, but not at the 9 weeks. DEX did not influence mRNA levels for IL-1β, 6, and 8, however, protein analysis indicated that IL-8 levels were lower in DEX treated joints. DEX resulted in significantly elevated expression of mRNA for MCP-1, leptin, and VEGF.

Conclusion: One IA administration of a glucocorticoid appears to mitigate the initial inflammation within the joint, but is not sufficient to protect the joint to 9 weeks post-surgery.

Keywords: Dexamethasone; Glucocorticoid; Inflammation; Infrapatellar fat pad; Knee injury; Rabbit model.

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / pathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use*
  • Female
  • Fibrosis
  • Injections, Intra-Articular
  • Knee Injuries / complications
  • Knee Injuries / drug therapy*
  • Knee Injuries / pathology
  • Knee Joint / drug effects
  • Knee Joint / pathology
  • Leptin / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Leptin
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Dexamethasone