Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effec...

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Autores principales:	Andrzej Steplewski, Jolanta Fertala, Ryan E Tomlinson, Mark L Wang, Allison Donahue, William V Arnold, Michael Rivlin, Pedro K Beredjiklian, Joseph A Abboud, Surena Namdari, Andrzej Fertala
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df5672a867184f4db745c8d3a4fd6ae5
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spelling	oai:doaj.org-article:df5672a867184f4db745c8d3a4fd6ae52021-12-02T20:14:48ZMechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.1932-620310.1371/journal.pone.0257147https://doaj.org/article/df5672a867184f4db745c8d3a4fd6ae52021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257147https://doaj.org/toc/1932-6203Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen-rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar formation in vivo. Here, we have utilized a clinically relevant arthrofibrosis model to study the broad mechanisms of the anti-scarring activity of this antibody. Moreover, we analyzed the effects of targeting collagen fibril formation on the quality of healed joint tissues, including the posterior capsule, patellar tendon, and subchondral bone. Our results show that blocking collagen fibrillogenesis not only reduces collagen content in the scar, but also accelerates the remodeling of healing tissues and changes the collagen fibrils' cross-linking. In total, this study demonstrated that targeting collagen fibrillogenesis to limit arthrofibrosis affects neither the quality of healing of the joint tissues nor disturbs vital tissues and organs.Andrzej SteplewskiJolanta FertalaRyan E TomlinsonMark L WangAllison DonahueWilliam V ArnoldMichael RivlinPedro K BeredjiklianJoseph A AbboudSurena NamdariAndrzej FertalaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257147 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrzej Steplewski Jolanta Fertala Ryan E Tomlinson Mark L Wang Allison Donahue William V Arnold Michael Rivlin Pedro K Beredjiklian Joseph A Abboud Surena Namdari Andrzej Fertala Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
description	Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen-rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar formation in vivo. Here, we have utilized a clinically relevant arthrofibrosis model to study the broad mechanisms of the anti-scarring activity of this antibody. Moreover, we analyzed the effects of targeting collagen fibril formation on the quality of healed joint tissues, including the posterior capsule, patellar tendon, and subchondral bone. Our results show that blocking collagen fibrillogenesis not only reduces collagen content in the scar, but also accelerates the remodeling of healing tissues and changes the collagen fibrils' cross-linking. In total, this study demonstrated that targeting collagen fibrillogenesis to limit arthrofibrosis affects neither the quality of healing of the joint tissues nor disturbs vital tissues and organs.
format	article
author	Andrzej Steplewski Jolanta Fertala Ryan E Tomlinson Mark L Wang Allison Donahue William V Arnold Michael Rivlin Pedro K Beredjiklian Joseph A Abboud Surena Namdari Andrzej Fertala
author_facet	Andrzej Steplewski Jolanta Fertala Ryan E Tomlinson Mark L Wang Allison Donahue William V Arnold Michael Rivlin Pedro K Beredjiklian Joseph A Abboud Surena Namdari Andrzej Fertala
author_sort	Andrzej Steplewski
title	Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
title_short	Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
title_full	Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
title_fullStr	Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
title_full_unstemmed	Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
title_sort	mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/df5672a867184f4db745c8d3a4fd6ae5
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Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.

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