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Does Pain at an Earlier Stage of Chondropathy Protect Female Mice Against Structural Progression After Surgically Induced Osteoarthritis?
Author(s) -
Loga Isabell S.,
Batchelor Vicky,
Driscoll Clare,
Burleigh Annika,
Chia ShiLu L.,
Stott Bryony,
MiotlaZarebska Jadwiga,
Riley David,
Dell’Accio Francesco,
Vincent Tonia L.
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41421
Subject(s) - chondropathy , osteoarthritis , stage (stratigraphy) , medicine , surgery , articular cartilage , pathology , biology , alternative medicine , paleontology
Objective Female C57BL/6 mice exhibit less severe chondropathy than male mice. This study was undertaken to test the robustness of this observation and explore underlying mechanisms. Methods Osteoarthritis was induced in male and female C57BL/6 or DBA/1 mice (n = 6–15 per group) by destabilization of the medial meniscus (DMM) or partial meniscectomy (PMX). Some mice were ovariectomized (OVX) (n = 30). In vivo repair after focal cartilage defect or joint immobilization (sciatic neurectomy) following DMM was assessed. Histologic analysis, evaluation of gene expression in whole knees, and behavioral analysis using Laboratory Animal Behavior Observation Registration and Analysis System (LABORAS) and Linton incapacitance testing (n = 7–10 mice per group) were performed. Results Female mice displayed less severe chondropathy (20–75% reduction) across both strains and after both surgeries. Activity levels after PMX were similar for male and female mice. Some repair‐associated genes were increased in female mouse joints after surgery, but no repair differences were evident in vivo. Despite reduced chondropathy, female mice developed pain‐like behavior at the same time as male mice. At the time of established pain‐like behavior (10 weeks after PMX), pain‐associated genes were significantly up‐regulated in female mice, including Gdnf (mean ± SEM fold change 2.54 ± 0.30), Nrtn (6.71 ± 1.24), Ntf3 (1.92 ± 0.27), and Ntf5 (2.89 ± 0.48) ( P < 0.01, P < 0.01, P < 0.05, and P < 0.001, respectively, versus male mice). Inflammatory genes were not regulated in painful joints in mice of either sex. Conclusion We confirm strong structural joint protection in female mice that is not due to activity or intrinsic repair differences. Female mice develop pain at the same time as males, but induce a distinct set of neurotrophins. We speculate that heightened pain sensitivity in female mice protects the joint by preventing overuse.