title: Single intra-articular dexamethasone injection immediately post-surgery in a rabbit model mitigates early inflammatory responses and post-traumatic osteoarthritis-like alterations.
abstract: Despite surgical reconstruction of the anterior cruciate ligament, a significant number of patients will still develop post-traumatic osteoarthritis (PTOA). Our objective was to determine if mitigating aspects of the acute phase of inflammation following a defined knee surgery with a single administration of a glucocorticoid could prevent the development of PTOA-like changes within an established rabbit model of surgically induced PTOA. An early and late post-surgical time-point was investigated in this study (48 h and 9 weeks post-surgery) in which the following groups were repeated (each n=6, for a total of 24 rabbits per time-point, and 48 rabbits used in the study): control (age/sex matched), sham (arthrotomy), drill injury (arthrotomy+two drill holes to a non-cartilaginous area of the femoral notch), and drill injury+single intra-articular (IA) injection of dexamethasone (DEX). At 48 h post-surgery, DEX treatment significantly lowered the mRNA levels for a subset of pro-inflammatory mediators, and significantly lowered the histological grade. Nine weeks post surgery, DEX treatment significantly lowered the histological scores (presented as effect size) for synovium (3.8), lateral femoral condyle (3.9), and lateral tibial cartilage (5.1) samples. Thus, DEX likely acts to prevent injury induced inflammation that could contribute to subsequent joint damage.
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Heard
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: Kristen I
authors.initials: KI
authors.lastname: Barton
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: May
authors.initials: M
authors.lastname: Chung
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Achari
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.|Department of Civil Engineering, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Shrive
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: Cyril B
authors.initials: CB
authors.lastname: Frank
authors.affiliation: Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction / Q000009:adverse effects / Q000379:methods*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D007249:Inflammation / Q000188:drug therapy*; D007269:Injections, Intra-Arterial; D010003:Osteoarthritis / Q000209:etiology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000517:prevention & control; D011184:Postoperative Period; D011817:Rabbits; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone
keywords: animal model; dexamethasone; glucocorticoid treatment; inflammation; post-traumatic osteoarthritis; synovitis; synovium