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Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

BACKGROUND AND PURPOSE: Corticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of...

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Autores principales: Rudnik‐Jansen, Imke, Tellegen, Anna R., Pouran, Behdad, Schrijver, Karin, Meij, Björn P., Emans, Pieter J., de Gendt, Erin, Thomas, Rachel E., Kik, Marja J.L., de Visser, Huub M., Weinans, Harrie, Egas, Annelies, van Maarseveen, Erik, Woike, Nina, Mihov, George, Thies, Jens, Tryfonidou, Marianna A., Creemers, Laura B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811746/
https://www.ncbi.nlm.nih.gov/pubmed/31378925
http://dx.doi.org/10.1111/bph.14817
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author Rudnik‐Jansen, Imke
Tellegen, Anna R.
Pouran, Behdad
Schrijver, Karin
Meij, Björn P.
Emans, Pieter J.
de Gendt, Erin
Thomas, Rachel E.
Kik, Marja J.L.
de Visser, Huub M.
Weinans, Harrie
Egas, Annelies
van Maarseveen, Erik
Woike, Nina
Mihov, George
Thies, Jens
Tryfonidou, Marianna A.
Creemers, Laura B.
author_facet Rudnik‐Jansen, Imke
Tellegen, Anna R.
Pouran, Behdad
Schrijver, Karin
Meij, Björn P.
Emans, Pieter J.
de Gendt, Erin
Thomas, Rachel E.
Kik, Marja J.L.
de Visser, Huub M.
Weinans, Harrie
Egas, Annelies
van Maarseveen, Erik
Woike, Nina
Mihov, George
Thies, Jens
Tryfonidou, Marianna A.
Creemers, Laura B.
author_sort Rudnik‐Jansen, Imke
collection PubMed
description BACKGROUND AND PURPOSE: Corticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations. EXPERIMENTAL APPROACH: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes. KEY RESULTS: Intra‐articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability‐induced OA cartilage degeneration, synovitis, nor the OA‐related bone phenotype was affected. However, biomaterial microsphere‐based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration. CONCLUSIONS AND IMPLICATIONS: We conclude that short‐term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage‐associated joint instability, but not of brief exposure.
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spelling pubmed-68117462019-10-30 Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing Rudnik‐Jansen, Imke Tellegen, Anna R. Pouran, Behdad Schrijver, Karin Meij, Björn P. Emans, Pieter J. de Gendt, Erin Thomas, Rachel E. Kik, Marja J.L. de Visser, Huub M. Weinans, Harrie Egas, Annelies van Maarseveen, Erik Woike, Nina Mihov, George Thies, Jens Tryfonidou, Marianna A. Creemers, Laura B. Br J Pharmacol Research Papers BACKGROUND AND PURPOSE: Corticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations. EXPERIMENTAL APPROACH: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes. KEY RESULTS: Intra‐articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability‐induced OA cartilage degeneration, synovitis, nor the OA‐related bone phenotype was affected. However, biomaterial microsphere‐based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration. CONCLUSIONS AND IMPLICATIONS: We conclude that short‐term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage‐associated joint instability, but not of brief exposure. John Wiley and Sons Inc. 2019-10-08 2019-10 /pmc/articles/PMC6811746/ /pubmed/31378925 http://dx.doi.org/10.1111/bph.14817 Text en © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Papers
Rudnik‐Jansen, Imke
Tellegen, Anna R.
Pouran, Behdad
Schrijver, Karin
Meij, Björn P.
Emans, Pieter J.
de Gendt, Erin
Thomas, Rachel E.
Kik, Marja J.L.
de Visser, Huub M.
Weinans, Harrie
Egas, Annelies
van Maarseveen, Erik
Woike, Nina
Mihov, George
Thies, Jens
Tryfonidou, Marianna A.
Creemers, Laura B.
Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
title Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
title_full Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
title_fullStr Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
title_full_unstemmed Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
title_short Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
title_sort local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811746/
https://www.ncbi.nlm.nih.gov/pubmed/31378925
http://dx.doi.org/10.1111/bph.14817
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