Overexpression of Peroxiredoxin 3 in Cartilage Reduces the Severity of Age-Related Osteoarthritis But Not Surgically Induced Osteoarthritis in Mice

Richard F. Loeser, Philip R. Coryell, Alexandra L Armstrong, John A. Collins, Priya Gopalakrishnan, Katie A. McDermott, Qitao Ran, Cathy S. Carlson

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Abstract

Objective: The study objective was to determine whether overexpression of the mitochondrial antioxidant peroxidase, peroxiredoxin 3 (Prx3), reduces the severity of osteoarthritis (OA) in mice. Methods: Age-related OA (age 18 and 24 months) and OA induced by destabilization of the medial meniscus (DMM at age 6 months) were assessed in male mice that overexpress a human Prdx3 transgene encoding the Prx3 protein. Lox-stop-lox-Prdx3 (iPrdx3) mice were crossed with aggrecan-CreERT2 mice to produce iPrdx3AgCreERT2 or with Col2Cre to produce iPrdx3Col2Cre mice. Germline transgenics (Prdx3Tg) were also evaluated. Prx3 protein level was assessed by immunoblotting and functionally after induction of elevated mitochondrial hydrogen peroxide (H2O2) using menadione. Histological sections of stifle joints were scored for cartilage damage (Articular Cartilage Structure score [ACS]), osteophytes, and synovial hyperplasia and were evaluated by histomorphometry. Results: Overexpression of Prx3 maintained mitochondrial membrane integrity and inhibited p38 phosphorylation in the presence of elevated H2O2. ACS scores of 18-month-old iPrdx3AgCreERT2 mice (mean ± SD, 4.88 ± 5.05) were significantly lower than age-matched iPrdx3 controls (11.75 ± 6.34, P = 0.002) and trended lower in the 18-month Prdx3Tg group (P = 0.14), whereas no significant differences between experimental and control groups at 24 months of age or in OA induced by DMM surgery were noted. Osteophyte scores trended lower in the 18-month-old Prdx3Tg group (P = 0.09) and at 24 months in the iPrdx3Col2Cre mice (P = 0.05). There were no significant group differences in synovial hyperplasia or histomorphometric measures. Conclusion: Overexpression of the mitochondrial peroxidase Prx3 reduced the severity of age-related OA, but not at advanced ages and not in DMM-induced OA in younger mice.

Original languageEnglish (US)
Pages (from-to)441-446
Number of pages6
JournalACR Open Rheumatology
Volume4
Issue number5
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
We thank Kathryn Kelley for technical assistance and Katalin Kovacs and Brea Pool for preparation of histologic sections.

Publisher Copyright:
© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

PubMed: MeSH publication types

  • Journal Article

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