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Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing

OBJECTIVES: Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and...

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Autores principales: Pilge, H., Fröbel, J., Prodinger, P. M., Mrotzek, S. J., Fischer, J. C., Zilkens, C., Bittersohl, B., Krauspe, R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852789/
https://www.ncbi.nlm.nih.gov/pubmed/26989119
http://dx.doi.org/10.1302/2046-3758.53.2000595
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author Pilge, H.
Fröbel, J.
Prodinger, P. M.
Mrotzek, S. J.
Fischer, J. C.
Zilkens, C.
Bittersohl, B.
Krauspe, R.
author_facet Pilge, H.
Fröbel, J.
Prodinger, P. M.
Mrotzek, S. J.
Fischer, J. C.
Zilkens, C.
Bittersohl, B.
Krauspe, R.
author_sort Pilge, H.
collection PubMed
description OBJECTIVES: Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. METHODS: We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. RESULTS: We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. CONCLUSIONS: Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595.
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spelling pubmed-48527892016-05-11 Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing Pilge, H. Fröbel, J. Prodinger, P. M. Mrotzek, S. J. Fischer, J. C. Zilkens, C. Bittersohl, B. Krauspe, R. Bone Joint Res Research OBJECTIVES: Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. METHODS: We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. RESULTS: We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. CONCLUSIONS: Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595. 2016-04-08 /pmc/articles/PMC4852789/ /pubmed/26989119 http://dx.doi.org/10.1302/2046-3758.53.2000595 Text en © 2016 Pilge et al. This is an open-access article distributed under the terms of the Creative Commons Attributions licence (CC -BY-MC), which permits unrestricted use, distribution, and reproduction in any medium, but not for commercial gain, provided the original author and source are credited.
spellingShingle Research
Pilge, H.
Fröbel, J.
Prodinger, P. M.
Mrotzek, S. J.
Fischer, J. C.
Zilkens, C.
Bittersohl, B.
Krauspe, R.
Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
title Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
title_full Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
title_fullStr Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
title_full_unstemmed Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
title_short Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
title_sort enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852789/
https://www.ncbi.nlm.nih.gov/pubmed/26989119
http://dx.doi.org/10.1302/2046-3758.53.2000595
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