title: The infrapatellar fat pad is affected by injury induced inflammation in the rabbit knee: use of dexamethasone to mitigate damage.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Heard
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Solbak
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: May
authors.initials: M
authors.lastname: Chung
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Achari
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.|Schulich School of Engineering, University of Calgary, Calgary, AB, Canada.
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Shrive
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.|Schulich School of Engineering, University of Calgary, Calgary, AB, Canada.
authors.forename: Cyril B
authors.initials: CB
authors.lastname: Frank
authors.affiliation: McCaig Institute for Bone and Joint Health, Biomedical Engineering Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. hartd@ucalgary.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005355:Fibrosis; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D020738:Leptin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D020738:Leptin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003907:Dexamethasone
keywords: Dexamethasone; Glucocorticoid; Inflammation; Infrapatellar fat pad; Knee injury; Rabbit model