Brigham Research Institute Poster Session Site logo-1
Close this search box.

Julie Mekhail



Job Title

Research Trainee

Academic Rank




Chilan B. G. Leite1 , Luciana P. Tavares2 , Julie Mekhail1 , Gergo Merkely1 , Janey Whalen1 , Julia F. Charles1 , Christian Lattermann1

Principal Investigator

Christian Lattermann

Research Category: Musculoskeletal/Orthopedics/Sports Medicine


Transection of the anterior cruciate ligament leads to production of specialized pro-resolving mediators

Scientific Abstract

Eight-week-old C57BL6/J mice underwent ACLT. Joint tissues were harvested from surgical and controlled unoperated contralateral knee at multiple time points. Periarticular synovial tissue expression of pro-inflammatory cytokines (TNF-α, IL-1β), SPM biosynthetic enzyme (12/15Alox) and receptors (LGR6, FPR2), and synovial fluid levels of MaR1 and RvD1 were measured by qPCR and ELISA, respectively. OARSI scoring was performed by blinded observers.

OARSI scoring at 8 weeks post-injury demonstrated that ACLT induces PTOA. Thus, we assessed the acute inflammatory and pro-resolving responses to ACL injury. ACLT induced acute inflammation with increased cellular infiltrate and induction of TNF-α/IL-1β expression in the first-week post-injury. Resolvin pathways were also induced. Joint injury induced local production of synovial fluid MaR1 and RvD1, with levels peaking 1 week after ACLT. Moreover, 12/15Alox and LGR6/FPR2 expression increase post-injury. Despite the induction of SPMs, evidence of chronic inflammation persisted through week 8.

Lay Abstract

Anterior cruciate ligament (ACL) tear leads to joint inflammation and osteochondral degeneration culminating in posttraumatic osteoarthritis (PTOA). Inflammation resolution is actively modulated by specialized pro-resolving mediators (SPMs), and fatty-acid derivatives with anti-inflammatory, analgesic, and regenerative properties. It is unknown whether SPMs play a role in PTOA. We investigated whether pro-resolving pathways are induced in a mouse model of ACL injury, focusing on maresin1 (MaR1) and resolvin D1 (RvD1), two omega-3-derived SPMs.

Clinical Implications

Injury in ACLT results in inflammation and induction of SPMs. Although the endogenous resolution response is insufficient to restore tissue homeostasis, the existence of these pathways suggests that exogenous SPMs could be a potential intervention to reduce damage after injury.