Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice

This article belongs to the Special Issue The Future of Cartilage Repair in Complex Biological Situations.

Detalles Bibliográficos
Autores: Tashkandi, Mustafa, Ali, Faiza, Alsaqer, Saqer, Alhousami, Thabet, Cano, Amparo, Martín, Alberto, Salvador, Fernando, Portillo, Francisco, Gerstenfeld, Louis C., Goldring, Mary B., Bais, Manish V.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/219283
Acceso en línea:http://hdl.handle.net/10261/219283
Access Level:acceso abierto
Palabra clave:Lysyl oxidase like-2
Osteoarthritis
Adenovirus delivery
Regeneration
Knee joint
Articular cartilage
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spelling Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in miceTashkandi, MustafaAli, FaizaAlsaqer, SaqerAlhousami, ThabetCano, AmparoMartín, AlbertoSalvador, FernandoPortillo, FranciscoGerstenfeld, Louis C.Goldring, Mary B.Bais, Manish V.Lysyl oxidase like-2OsteoarthritisAdenovirus deliveryRegenerationKnee jointArticular cartilageThis article belongs to the Special Issue The Future of Cartilage Repair in Complex Biological Situations.[Background]: The goal of this study was to determine if adenovirus-delivered LOXL2 protects against progressive knee osteoarthritis (OA), assess its specific mechanism of action; and determine if the overexpression of LOXL2 in transgenic mice can protect against the development of OA-related cartilage damage and joint disability. Methods: Four-month-old Cho/+ male and female mice were intraperitoneally injected with either Adv-RFP-LOXL2 or an empty vector twice a month for four months. The proteoglycan levels and the expression of anabolic and catabolic genes were examined by immunostaining and qRT-PCR. The effect of LOXL2 expression on signaling was tested via the pro-inflammatory cytokine IL1β in the cartilage cell line ATDC5. Finally; the OA by monosodium iodoacetate (MIA) injection was also induced in transgenic mice with systemic overexpression of LOXL2 and examined gene expression and joint function by treadmill tests and assessment of allodynia.[Results]: The adenovirus treatment upregulated LOXL2; Sox9; Acan and Runx2 expression in both males and females. The Adv-RFP-LOXL2 injection; but not the empty vector injection increased proteoglycan staining and aggrecan expression but reduced MMP13 expression. LOXL2 attenuated IL-1β-induced phospho-NF-κB/p65 and rescued chondrogenic lineage-related genes in ATDC5 cells; demonstrating one potential protective mechanism. LOXL2 attenuated phospho-NF-κB independent of its enzymatic activity. Finally; LOXL2-overexpressing transgenic mice were protected from MIA-induced OA-related functional changes; including the time and distance traveled on the treadmill and allodynia.[Conclusion]: Our study demonstrates that systemic LOXL2 adenovirus or LOXL2 genetic overexpression in mice can protect against OA. These findings demonstrate the potential for LOXL2 gene therapy for knee-OA clinical treatment in the future.The authors acknowledge NIH/NIDCR grants R03DE025274 and R21DE026892 as well as CTSI pilot funding to Manish V. Bais.Peer reviewedMultidisciplinary Digital Publishing InstituteNational Institutes of Health (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/219283reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/ijms20194798Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2192832026-05-22T06:33:51Z
dc.title.none.fl_str_mv Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
title Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
spellingShingle Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
Tashkandi, Mustafa
Lysyl oxidase like-2
Osteoarthritis
Adenovirus delivery
Regeneration
Knee joint
Articular cartilage
title_short Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
title_full Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
title_fullStr Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
title_full_unstemmed Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
title_sort Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice
dc.creator.none.fl_str_mv Tashkandi, Mustafa
Ali, Faiza
Alsaqer, Saqer
Alhousami, Thabet
Cano, Amparo
Martín, Alberto
Salvador, Fernando
Portillo, Francisco
Gerstenfeld, Louis C.
Goldring, Mary B.
Bais, Manish V.
author Tashkandi, Mustafa
author_facet Tashkandi, Mustafa
Ali, Faiza
Alsaqer, Saqer
Alhousami, Thabet
Cano, Amparo
Martín, Alberto
Salvador, Fernando
Portillo, Francisco
Gerstenfeld, Louis C.
Goldring, Mary B.
Bais, Manish V.
author_role author
author2 Ali, Faiza
Alsaqer, Saqer
Alhousami, Thabet
Cano, Amparo
Martín, Alberto
Salvador, Fernando
Portillo, Francisco
Gerstenfeld, Louis C.
Goldring, Mary B.
Bais, Manish V.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Institutes of Health (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Lysyl oxidase like-2
Osteoarthritis
Adenovirus delivery
Regeneration
Knee joint
Articular cartilage
topic Lysyl oxidase like-2
Osteoarthritis
Adenovirus delivery
Regeneration
Knee joint
Articular cartilage
description This article belongs to the Special Issue The Future of Cartilage Repair in Complex Biological Situations.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/219283
url http://hdl.handle.net/10261/219283
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/ijms20194798
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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