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Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing

BACKGROUND: Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the earl...

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Autores principales: Caetano-Lopes, Joana, Lopes, Ana, Rodrigues, Ana, Fernandes, Diana, Perpétuo, Inês P., Monjardino, Teresa, Lucas, Raquel, Monteiro, Jacinto, Konttinen, Yrjö T., Canhão, Helena, Fonseca, João E.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037947/
https://www.ncbi.nlm.nih.gov/pubmed/21347301
http://dx.doi.org/10.1371/journal.pone.0016947
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author Caetano-Lopes, Joana
Lopes, Ana
Rodrigues, Ana
Fernandes, Diana
Perpétuo, Inês P.
Monjardino, Teresa
Lucas, Raquel
Monteiro, Jacinto
Konttinen, Yrjö T.
Canhão, Helena
Fonseca, João E.
author_facet Caetano-Lopes, Joana
Lopes, Ana
Rodrigues, Ana
Fernandes, Diana
Perpétuo, Inês P.
Monjardino, Teresa
Lucas, Raquel
Monteiro, Jacinto
Konttinen, Yrjö T.
Canhão, Helena
Fonseca, João E.
author_sort Caetano-Lopes, Joana
collection PubMed
description BACKGROUND: Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13); between the 4(th) and 7(th) day (n = 33); and after one week from the fracture (n = 10). Inflammation- and bone metabolism-related genes were assessed at the fracture site. The expression of pro-inflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4(th)–7(th) days after fracture. Sclerostin expression diminished during the first days after fracture. CONCLUSIONS: The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing.
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spelling pubmed-30379472011-02-23 Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing Caetano-Lopes, Joana Lopes, Ana Rodrigues, Ana Fernandes, Diana Perpétuo, Inês P. Monjardino, Teresa Lucas, Raquel Monteiro, Jacinto Konttinen, Yrjö T. Canhão, Helena Fonseca, João E. PLoS One Research Article BACKGROUND: Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13); between the 4(th) and 7(th) day (n = 33); and after one week from the fracture (n = 10). Inflammation- and bone metabolism-related genes were assessed at the fracture site. The expression of pro-inflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4(th)–7(th) days after fracture. Sclerostin expression diminished during the first days after fracture. CONCLUSIONS: The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing. Public Library of Science 2011-02-11 /pmc/articles/PMC3037947/ /pubmed/21347301 http://dx.doi.org/10.1371/journal.pone.0016947 Text en Caetano-Lopes et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Caetano-Lopes, Joana
Lopes, Ana
Rodrigues, Ana
Fernandes, Diana
Perpétuo, Inês P.
Monjardino, Teresa
Lucas, Raquel
Monteiro, Jacinto
Konttinen, Yrjö T.
Canhão, Helena
Fonseca, João E.
Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing
title Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing
title_full Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing
title_fullStr Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing
title_full_unstemmed Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing
title_short Upregulation of Inflammatory Genes and Downregulation of Sclerostin Gene Expression Are Key Elements in the Early Phase of Fragility Fracture Healing
title_sort upregulation of inflammatory genes and downregulation of sclerostin gene expression are key elements in the early phase of fragility fracture healing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037947/
https://www.ncbi.nlm.nih.gov/pubmed/21347301
http://dx.doi.org/10.1371/journal.pone.0016947
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