Transcriptomic changes in porcine articular cartilage 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, United States of America., Karamchedu NP; Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, United States of America., Proffen BL; Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America., Molino J; Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, United States of America., Fleming BC; Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, United States of America., Murray MM; Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 May 03; Vol. 18 (5), pp. e0284777. Date of Electronic Publication: 2023 May 03 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0284777
Abstrakt: To determine the transcriptomic changes seen in early- to mid-stage posttraumatic osteoarthritis (PTOA) development, 72 Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair, followed by articular cartilage harvesting and RNA-sequencing at three different postoperative timepoints (1, 4, and 52 weeks). Six additional subjects received no ligament transection and provided cartilage tissue to serve as controls. Differential gene expression analysis between post-transection cartilage and healthy cartilage revealed an initial increase in transcriptomic differences at 1 and 4 weeks followed by a stark reduction in transcriptomic differences at 52 weeks. This analysis also showed how different treatments genetically modulate the course of PTOA following ligament disruption. Specific genes (e.g., MMP1, POSTN, IGF1, PTGFR, HK1) were identified as being upregulated in the cartilage of injured subjects across all timepoints regardless of treatment. At the 52-week timepoint, 4 genes (e.g., A4GALT, EFS, NPTXR, ABCA3) that-as far as we know-have yet to be associated with PTOA were identified as being concordantly differentially expressed across all treatment groups when compared to controls. Functional pathway analysis of injured subject cartilage compared to control cartilage revealed overarching patterns of cellular proliferation at 1 week, angiogenesis, ECM interaction, focal adhesion, and cellular migration at 4 weeks, and calcium signaling, immune system activation, GABA signaling, and HIF-1 signaling at 52 weeks.
Competing Interests: 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. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2023 Donnenfield et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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