Early ablation of Ccr2 in aggrecan-expressing cells following knee injury ameliorates joint damage and pain during post-traumatic osteoarthritis.
Animal model
Bone
Cartilage
Chemokines
Joint disease
Osteoarthritis
Journal
Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
12
11
2021
revised:
10
08
2022
accepted:
26
08
2022
pubmed:
9
9
2022
medline:
22
11
2022
entrez:
8
9
2022
Statut:
ppublish
Résumé
To investigate whether Ccr2 inactivation in aggrecan-expressing cells induced before post-traumatic OA (PTOA) onset or during progression, improves joint structures, synovial thickness and pain. We induced a Ccr2 deletion in aggrecan-expressing cells (CCR2-AggKO) in skeletally mature mice using a tamoxifen-inducible Ccr2 inactivation. We stimulated PTOA changes (destabilization of medial meniscus, DMM) in CCR2-AggKO and CCR2+/+ mice, inducing recombination before DMM or 4 wks after DMM (early-vs late-inactivation). Joint damage was evaluated 2, 4, 8, 12 wks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous (incapacitance meter) and evoked pain (von-Frey filaments) were assessed up to 20 wks. Early aggrecan-Ccr2 inactivation in CCR2-AggKO mice (N=8) resulted in improved ACS score (8-12wk, P=0.002), AC area (4-12wk, P<0.05) and Saf-O score (2wks P=0.004, 4wks P=0.02, 8-12wks P=0.002) compared to CCR2+/+. Increased subchondral bone thickness was delayed only at 2 wks and exclusively following early recombination. Osteophyte size was not affected, but osteophyte maturation (cartilage-to-bone) was delayed (4wks P=0.04; 8 wks P=0.03). Although late aggrecan-Ccr2 deletion led to some cartilage improvement, most data did not reach statistical significance; osteophyte maturity was delayed at 12wks. Early aggrecan-Ccr2 deletion led to improved pain measures of weight bearing compared to CCR2+/+ mice (N = 9, 12wks diff 0.13 [0.01, 0.26], 16wks diff 0.15 [0.05, 0.26], 20wks diff 0.23 [0.14, 0.31]). Improved mechanosensitivity in evoked pain, although less noticeable, was detected. We demonstrated that deletion of Ccr2 in aggrecan expressing cells reduces the initiation but not progression of OA.
Identifiants
pubmed: 36075514
pii: S1063-4584(22)00833-0
doi: 10.1016/j.joca.2022.08.015
pmc: PMC9671864
mid: NIHMS1841834
pii:
doi:
Substances chimiques
Aggrecans
0
Ccr2 protein, mouse
0
Receptors, CCR2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1616-1630Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR072580
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070821
Pays : United States
Informations de copyright
Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Références
Dev Cell. 2012 Jul 17;23(1):71-81
pubmed: 22814601
Biomed Res Int. 2014;2014:606870
pubmed: 25045687
Biomacromolecules. 2007 Dec;8(12):3879-85
pubmed: 18039001
Lancet Rheumatol. 2021 Jun 24;3(9):e648-e658
pubmed: 34476411
J Orthop Res. 2017 Apr;35(4):735-739
pubmed: 27808445
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20602-7
pubmed: 23185004
Best Pract Res Clin Rheumatol. 2017 Oct;31(5):676-687
pubmed: 30509413
J Cell Physiol. 2019 Jul;234(7):11176-11187
pubmed: 30456760
Ann Rheum Dis. 2007 Jan;66(1):86-91
pubmed: 16877532
Eur J Pain. 2011 Sep;15(8):843.e1-14
pubmed: 21315627
J Rheumatol. 2000 Apr;27(4):1005-19
pubmed: 10782830
Eur Cell Mater. 2011 Feb 24;21:202-20
pubmed: 21351054
Arthritis Rheumatol. 2014 Dec;66(12):3337-48
pubmed: 25200274
Osteoarthritis Cartilage. 2021 Dec;29(12):1732-1740
pubmed: 34536530
Sci Rep. 2020 Jun 22;10(1):10077
pubmed: 32572077
Nat Rev Rheumatol. 2013 Nov;9(11):654-64
pubmed: 24045707
Arthritis Rheum. 2004 Aug;50(8):2547-58
pubmed: 15334469
J Bone Miner Res. 2015 Feb;30(2):286-96
pubmed: 25088728
Scand J Immunol. 2018 Dec;88(6):e12722
pubmed: 30403025
Calcif Tissue Int. 2013 Jun;92(6):566-75
pubmed: 23460341
Osteoarthritis Cartilage. 2003 Nov;11(11):821-30
pubmed: 14609535
Osteoarthritis Cartilage. 2018 Sep;26(9):1257-1261
pubmed: 29723633
Arthritis Rheumatol. 2017 Feb;69(2):352-361
pubmed: 27564840
Osteoarthritis Cartilage. 2017 Mar;25(3):406-412
pubmed: 27746376
Arthritis Rheum. 2009 Dec;60(12):3723-33
pubmed: 19950295
J Immunol. 2004 Jan 15;172(2):890-8
pubmed: 14707060
Ann Rheum Dis. 2017 May;76(5):914-922
pubmed: 27965260
Arthritis Rheumatol. 2015 Oct;67(10):2691-701
pubmed: 26138996
Genesis. 2009 Dec;47(12):805-14
pubmed: 19830818
Chem Immunol. 1999;72:30-41
pubmed: 10550928
Arthritis Rheumatol. 2016 Sep;68(9):2129-40
pubmed: 26991527
J Immunol Methods. 2001 Mar 1;249(1-2):155-65
pubmed: 11226473
Osteoarthritis Cartilage. 2017 Jun;25(6):799-801
pubmed: 28189827
Blood. 2012 Jul 19;120(3):613-25
pubmed: 22577176
Osteoarthritis Cartilage. 2017 Jun;25(6):914-925
pubmed: 27856294
J Rheumatol. 2005 Jun;32(6):1156-8; discussion 1158-9
pubmed: 15977355
Ann Clin Biochem. 2015 Mar;52(Pt 2):276-82
pubmed: 25005456
Nat Med. 2009 Apr;15(4):417-24
pubmed: 19330010
Cartilage. 2011 Oct;2(4):354-63
pubmed: 26069594
Osteoarthritis Cartilage. 2007 Sep;15(9):1061-9
pubmed: 17470400
Biomaterials. 2013 Oct;34(32):8002-11
pubmed: 23891396
BMJ. 2009 Aug 21;339:b2844
pubmed: 19700505
Arthritis Rheumatol. 2015 Jul;67(7):1826-36
pubmed: 25776267
Nature. 2005 Mar 31;434(7033):644-8
pubmed: 15800624
Int J Biochem Cell Biol. 2012 May;44(5):690-3
pubmed: 22297263
J Clin Invest. 2004 Mar;113(6):856-66
pubmed: 15067318
Osteoarthritis Cartilage. 2021 May;29(5):728-738
pubmed: 33609695
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7947-52
pubmed: 12808141
Nat Rev Rheumatol. 2011 Jan;7(1):33-42
pubmed: 21119608