Post-traumatic osteoarthritis progression is diminished by early mechanical unloading and anti-inflammatory treatment in mice. Issue 12 (December 2021)

• Record Type: Journal Article
• Authors: Hsia, A.W.; Jbeily, E.H.; Mendez, M.E.; Cunningham, H.C.; Biris, K.K.; Bang, H.; Lee, C.A.; Loots, G.G.; Christiansen, B.A.
• Is Part Of: Osteoarthritis and cartilage. Volume 29:Issue 12(2021)
• Page Start: 1709
• Page End: 1719
• Publication Date: 2021-12
• Subjects: Post-traumatic osteoarthritis -- ACL Injury -- Hindlimb unloading -- Osteophytes -- Subchondral bone -- COX-2 -- NSAID -- Synovitis; Osteoarthritis -- Periodicals; Cartilage -- Periodicals; Osteoarthritis -- Periodicals; Cartilage -- Periodicals; Arthrose -- Périodiques; Articulations -- Maladies -- Périodiques; 616.7223005
• DOI: 10.1016/j.joca.2021.09.014
• Languages: English
• ISSNs: 1063-4584

Abstract

Summary: Objective: Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0–7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression. Design: Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury. Results: HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: −46%, CXB: −30%, HLU + CXB: −35% relative to vehicle GC at day 28). Conclusions: These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.