Microscopic and transcriptomic changes in porcine synovium one year following disruption of the anterior cruciate ligament.

Autor: Donnenfield JI; Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jonah_donnenfield@hms.harvard.edu., Fleming BC; Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, USA. Electronic address: braden_fleming@brown.edu., Proffen BL; Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: benedikt.proffen@childrens.harvard.edu., Podury A; Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. Electronic address: archana_podury@hms.harvard.edu., Murray MM; Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: martha.murray@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2023 Dec; Vol. 31 (12), pp. 1554-1566. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1016/j.joca.2023.07.014
Abstrakt: Objective: There is no disease-modifying treatment for posttraumatic osteoarthritis (PTOA). This may be partly due to an incomplete understanding of synovitis, which has been causally linked to PTOA progression. The microscopic and transcriptomic changes in synovium seen in early- to mid-stage PTOA were evaluated to better characterize this knowledge gap.
Methods: Seventy-two Yucatan minipigs underwent transection of the anterior cruciate ligament (ACL). Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair, followed by microscopic synovium evaluation and RNA-sequencing at 1, 4, and 52 weeks. Six additional subjects received no ligament transection and served as 1- and 4-week controls and 12 contralateral knees served as 52-week controls.
Results: Synovial lining thickness, stromal cellularity, and overall microscopic synovitis reached their highest levels in the first few weeks following injury. Inflammatory infiltration continued to increase over the course of a year. Leaving the ACL transected, reconstructing the ligament, or repairing the ligament did not modulate synovitis development at 1, 4, or 52 weeks. Differential gene expression analysis of PTOA-affected synovium compared to control synovium revealed increased cell proliferation, angiogenesis, collagen breakdown, and diminished lipid metabolism at 1 and 4 weeks, and increased axonogenesis and focal adhesion with reduced immune activation at 52 weeks.
Conclusions: Synovitis was present one year after ACL injury and was not alleviated by surgical intervention. Gene expression in early synovitis was characterized by cell proliferation, angiogenesis, proteolysis, and reduced lipolysis, which was followed by nerve growth and cellular adhesion with less immune activation at 52 weeks.
Competing Interests: Declaration of Competing Interest Dr. Murray is a founder and equity holder, Dr. Proffen is a paid consultant and equity holder, and Dr. Fleming is a founder of Miach Orthopaedics, Inc., which was formed to upscale production of a scaffold for ACL restoration and is related to one of the ACL procedures described herein. Drs. Murray and Proffen maintain a conflict-of-interest management plan approved by Boston Children’s Hospital and Harvard Medical School. Dr. Fleming maintains a conflict-of-interest management plan with Rhode Island Hospital.
(Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: