RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice

ABSTRACT The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant lo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kathleen Turajane, Gang Ji, Yurii Chinenov, Max Chao, Ugur Ayturk, Vincentius J Suhardi, Matthew B Greenblatt, Lionel B Ivashkiv, Mathias PG Bostrom, Xu Yang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	AGING CELL/TISSUE SIGNALING – PARACRINE PATHWAYS IMPLANTS MOLECULAR PATHWAYS – REMODELING PRECLINICAL STUDIES Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/13550411305d4aa78cf03b5857af3ac9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:13550411305d4aa78cf03b5857af3ac9
record_format	dspace
spelling	oai:doaj.org-article:13550411305d4aa78cf03b5857af3ac92021-11-04T12:00:57ZRNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice2473-403910.1002/jbm4.10535https://doaj.org/article/13550411305d4aa78cf03b5857af3ac92021-11-01T00:00:00Zhttps://doi.org/10.1002/jbm4.10535https://doaj.org/toc/2473-4039ABSTRACT The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri‐implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone‐implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone‐implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri‐implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri‐implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Kathleen TurajaneGang JiYurii ChinenovMax ChaoUgur AyturkVincentius J SuhardiMatthew B GreenblattLionel B IvashkivMathias PG BostromXu YangWileyarticleAGINGCELL/TISSUE SIGNALING – PARACRINE PATHWAYSIMPLANTSMOLECULAR PATHWAYS – REMODELINGPRECLINICAL STUDIESOrthopedic surgeryRD701-811Diseases of the musculoskeletal systemRC925-935ENJBMR Plus, Vol 5, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AGING CELL/TISSUE SIGNALING – PARACRINE PATHWAYS IMPLANTS MOLECULAR PATHWAYS – REMODELING PRECLINICAL STUDIES Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
spellingShingle	AGING CELL/TISSUE SIGNALING – PARACRINE PATHWAYS IMPLANTS MOLECULAR PATHWAYS – REMODELING PRECLINICAL STUDIES Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935 Kathleen Turajane Gang Ji Yurii Chinenov Max Chao Ugur Ayturk Vincentius J Suhardi Matthew B Greenblatt Lionel B Ivashkiv Mathias PG Bostrom Xu Yang RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice
description	ABSTRACT The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri‐implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone‐implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone‐implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri‐implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri‐implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
format	article
author	Kathleen Turajane Gang Ji Yurii Chinenov Max Chao Ugur Ayturk Vincentius J Suhardi Matthew B Greenblatt Lionel B Ivashkiv Mathias PG Bostrom Xu Yang
author_facet	Kathleen Turajane Gang Ji Yurii Chinenov Max Chao Ugur Ayturk Vincentius J Suhardi Matthew B Greenblatt Lionel B Ivashkiv Mathias PG Bostrom Xu Yang
author_sort	Kathleen Turajane
title	RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice
title_short	RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice
title_full	RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice
title_fullStr	RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice
title_full_unstemmed	RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice
title_sort	rna‐seq analysis of peri‐implant tissue shows differences in immune, notch, wnt, and angiogenesis pathways in aged versus young mice
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/13550411305d4aa78cf03b5857af3ac9
work_keys_str_mv	AT kathleenturajane rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT gangji rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT yuriichinenov rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT maxchao rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT ugurayturk rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT vincentiusjsuhardi rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT matthewbgreenblatt rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT lionelbivashkiv rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT mathiaspgbostrom rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice AT xuyang rnaseqanalysisofperiimplanttissueshowsdifferencesinimmunenotchwntandangiogenesispathwaysinagedversusyoungmice
_version_	1718444883874676736

RNA‐seq Analysis of Peri‐Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice

Ejemplares similares