Neonatal Enthesis Healing Involves Noninflammatory Acellular Scar Formation through Extracellular Matrix Secretion by Resident Cells.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
03
01
2022
revised:
19
04
2022
accepted:
04
05
2022
pubmed:
7
6
2022
medline:
17
8
2022
entrez:
6
6
2022
Statut:
ppublish
Résumé
Wound healing typically recruits the immune and vascular systems to restore tissue structure and function. However, injuries to the enthesis, a hypocellular and avascular tissue, often result in fibrotic scar formation and loss of mechanical properties, severely affecting musculoskeletal function and life quality. This raises questions about the healing capabilities of the enthesis. Herein, this study established an injury model to the Achilles entheses of neonatal mice to study the effectiveness of early-age enthesis healing. Histology and immunohistochemistry analyses revealed an atypical process that did not involve inflammation or angiogenesis. Instead, healing was mediated by secretion of collagen types I and II by resident cells, which formed a permanent hypocellular and avascular scar. Transmission electron microscopy showed that the cellular response to injury, including endoplasmic reticulum stress, autophagy, and cell death, varied between the tendon and cartilage ends of the enthesis. Single-molecule in situ hybridization, immunostaining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays verified these differences. Finally, gait analysis showed that these processes effectively restored function of the injured leg. These findings reveal a novel healing mechanism in neonatal entheses, whereby local extracellular matrix secretion by resident cells forms an acellular extracellular matrix deposit without inflammation, allowing gait restoration. These insights into the healing mechanism of a complex transitional tissue may lead to new therapeutic strategies for adult enthesis injuries.
Identifiants
pubmed: 35659946
pii: S0002-9440(22)00151-1
doi: 10.1016/j.ajpath.2022.05.008
pmc: PMC9379688
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1122-1135Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR055580
Pays : United States
Informations de copyright
Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Références
J Anat. 2006 Apr;208(4):471-90
pubmed: 16637873
Osteoarthritis Cartilage. 2002 Jun;10(6):432-63
pubmed: 12056848
Spine (Phila Pa 1976). 2009 Jan 15;34(2):131-40
pubmed: 19139663
Brain Behav. 2017 May 18;7(7):e00723
pubmed: 28729931
J Bone Joint Surg Am. 2018 Aug 15;100(16):e109
pubmed: 30106830
J Musculoskelet Neuronal Interact. 2005 Mar;5(1):35-40
pubmed: 15788869
J Orthop Res. 2018 Dec;36(12):3275-3284
pubmed: 30084210
Muscles Ligaments Tendons J. 2014 Nov 17;4(3):333-42
pubmed: 25489552
Methods Mol Biol. 2014;1130:149-164
pubmed: 24482171
Cell Rep. 2020 Nov 24;33(8):108408
pubmed: 33238125
Sci Rep. 2017 Mar 23;7:45238
pubmed: 28332620
Clin Dermatol. 2007 Jan-Feb;25(1):9-18
pubmed: 17276196
Apoptosis. 2014 Oct;19(10):1471-83
pubmed: 25015553
J Anat. 2017 Jul;231(1):129-139
pubmed: 28436567
Materials (Basel). 2013 Feb 22;6(2):637-668
pubmed: 28809332
FASEB J. 2018 Sep;32(9):4753-4762
pubmed: 29570392
Cell Death Differ. 2004 Apr;11(4):372-80
pubmed: 14765132
BMC Med. 2011 May 31;9:66
pubmed: 21627784
Annu Rev Pathol. 2008;3:399-425
pubmed: 18039139
Apoptosis. 2010 May;15(5):631-8
pubmed: 20091349
Development. 2018 Jun 26;145(12):
pubmed: 29945988
Immunol Today. 1994 Oct;15(10):490-5
pubmed: 7945775
J Orthop Res. 2002 May;20(3):454-63
pubmed: 12038618
Science. 2011 Feb 25;331(6020):1078-80
pubmed: 21350179
J Neurosci Methods. 2007 Aug 15;164(1):120-30
pubmed: 17532474
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Musculoskelet Neuronal Interact. 2010 Mar;10(1):35-45
pubmed: 20190378
BMC Bioinformatics. 2021 Sep 10;22(1):433
pubmed: 34507520
Osteoarthritis Cartilage. 1999 Jan;7(1):130-40
pubmed: 10367021
Adv Drug Deliv Rev. 2015 Apr;84:222-39
pubmed: 25446135
Physiol Rev. 2004 Jan;84(1):209-38
pubmed: 14715915
Int J Mol Sci. 2015 Oct 30;16(11):26035-54
pubmed: 26528972
Biores Open Access. 2017 Jun 01;6(1):47-57
pubmed: 28736687
Development. 2017 Apr 1;144(7):1159-1164
pubmed: 28219952
Dev Biol. 2008 Mar 1;315(1):125-35
pubmed: 18234177
Dev Cell. 2021 Jun 21;56(12):1712-1726.e6
pubmed: 34081908
Neuron. 2012 Jul 26;75(2):294-305
pubmed: 22841314
Bone Joint Res. 2017 Apr;6(4):231-244
pubmed: 28450316
J Cell Physiol. 2017 Nov;232(11):2977-2984
pubmed: 28067409
Cell Death Dis. 2017 Oct 12;8(10):e3116
pubmed: 29022912
J Orthop Res. 2015 Jun;33(6):832-9
pubmed: 25641114
Bone. 2013 Jul;55(1):44-51
pubmed: 23542869
Cell Death Differ. 2007 Sep;14(9):1576-82
pubmed: 17612585
Elife. 2013 Sep 24;2:e01004
pubmed: 24066226
Nat Rev Immunol. 2010 Dec;10(12):826-37
pubmed: 21088683
Dev Cell. 2021 Jun 21;56(12):1700-1711.e8
pubmed: 34081909
Methods Mol Biol. 2014;1130:203-215
pubmed: 24482175
Apoptosis. 2005 Oct;10(5):1105-10
pubmed: 16151643
Methods Enzymol. 2009;452:13-23
pubmed: 19200873
J Orthop Res. 2007 Sep;25(9):1121-7
pubmed: 17469197
Eur Cell Mater. 2005 Apr 14;9:23-32; discussion 23-32
pubmed: 15830323
Dev Cell. 2009 Dec;17(6):861-73
pubmed: 20059955
J Bone Joint Surg Am. 2021 May 5;103(9):e36
pubmed: 33475308
Apoptosis. 2004 May;9(3):265-77
pubmed: 15258458
Autophagy. 2015 Nov 2;11(11):1956-1977
pubmed: 26389781
Methods Mol Biol. 2021;2230:231-257
pubmed: 33197018
Birth Defects Res C Embryo Today. 2014 Mar;102(1):101-12
pubmed: 24677726
Cell Death Differ. 2018 Mar;25(3):486-541
pubmed: 29362479
PLoS One. 2014 Apr 23;9(4):e96113
pubmed: 24759953
Mol Cell. 2018 Jan 18;69(2):169-181
pubmed: 29107536
Eur Spine J. 2016 Jan;25(1):80-95
pubmed: 26188769
Eur J Immunol. 1981 Oct;11(10):805-15
pubmed: 7308288
Annu Rev Biomed Eng. 2012;14:47-71
pubmed: 22809137
J Orthop Res. 2021 Aug;39(8):1789-1799
pubmed: 32497311
Osteoarthritis Cartilage. 1999 Jan;7(1):15-28
pubmed: 10367012
Am J Sports Med. 1998 Mar-Apr;26(2):309-24
pubmed: 9548130