Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue

The demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain. Fibroblasts can modulate the production of the various components of the extracellular matrix, according to type of stimuli: physical, mechanical, hormonal, a...

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Main Authors: Caterina Fede, Carmelo Pirri, Lucia Petrelli, Diego Guidolin, Chenglei Fan, Raffaele De Caro, Carla Stecco
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/8/2936
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author Caterina Fede
Carmelo Pirri
Lucia Petrelli
Diego Guidolin
Chenglei Fan
Raffaele De Caro
Carla Stecco
author_facet Caterina Fede
Carmelo Pirri
Lucia Petrelli
Diego Guidolin
Chenglei Fan
Raffaele De Caro
Carla Stecco
author_sort Caterina Fede
collection DOAJ
description The demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain. Fibroblasts can modulate the production of the various components of the extracellular matrix, according to type of stimuli: physical, mechanical, hormonal, and pharmacological. In this work, fascial fibroblasts were isolated from small samples of human fascia lata of the thigh, collected from three volunteer patients (two men, one woman) during orthopedic surgery. This text demonstrates for the first time that the agonist of cannabinoid receptor 2, HU-308, can lead to in vitro production of hyaluronan-rich vesicles only 3–4 h after treatment, being rapidly released into the extracellular environment. We demonstrated that these vesicles are rich in hyaluronan after Alcian blue and Toluidine blue stainings, immunocytochemistry, and transmission electron microscopy. In addition, incubation with the antagonist AM630 blocked vesicles production by cells, confirming that release of hyaluronan is a cannabinoid-mediated effect. These results may show how fascial cells respond to the endocannabinoid system by regulating and remodeling the formation of the extracellular matrix. This is a first step in our understanding of how therapeutic applications of cannabinoids to treat pain may also have a peripheral effect, altering the biosynthesis of the extracellular matrix in fasciae and, consequently, remodeling the tissue and its properties.
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spelling doaj.art-d2bab1764a0640ebac08a0c07b0ed5a92023-11-19T22:21:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218293610.3390/ijms21082936Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial TissueCaterina Fede0Carmelo Pirri1Lucia Petrelli2Diego Guidolin3Chenglei Fan4Raffaele De Caro5Carla Stecco6Department of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyDepartment of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyDepartment of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyDepartment of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyDepartment of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyDepartment of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyDepartment of Neurosciences, Institute of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, ItalyThe demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain. Fibroblasts can modulate the production of the various components of the extracellular matrix, according to type of stimuli: physical, mechanical, hormonal, and pharmacological. In this work, fascial fibroblasts were isolated from small samples of human fascia lata of the thigh, collected from three volunteer patients (two men, one woman) during orthopedic surgery. This text demonstrates for the first time that the agonist of cannabinoid receptor 2, HU-308, can lead to in vitro production of hyaluronan-rich vesicles only 3–4 h after treatment, being rapidly released into the extracellular environment. We demonstrated that these vesicles are rich in hyaluronan after Alcian blue and Toluidine blue stainings, immunocytochemistry, and transmission electron microscopy. In addition, incubation with the antagonist AM630 blocked vesicles production by cells, confirming that release of hyaluronan is a cannabinoid-mediated effect. These results may show how fascial cells respond to the endocannabinoid system by regulating and remodeling the formation of the extracellular matrix. This is a first step in our understanding of how therapeutic applications of cannabinoids to treat pain may also have a peripheral effect, altering the biosynthesis of the extracellular matrix in fasciae and, consequently, remodeling the tissue and its properties.https://www.mdpi.com/1422-0067/21/8/2936fasciahyaluronanvesiclesendocannabinoidagonistantagonist
spellingShingle Caterina Fede
Carmelo Pirri
Lucia Petrelli
Diego Guidolin
Chenglei Fan
Raffaele De Caro
Carla Stecco
Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue
International Journal of Molecular Sciences
fascia
hyaluronan
vesicles
endocannabinoid
agonist
antagonist
title Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue
title_full Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue
title_fullStr Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue
title_full_unstemmed Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue
title_short Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue
title_sort sensitivity of the fasciae to the endocannabinoid system production of hyaluronan rich vesicles and potential peripheral effects of cannabinoids in fascial tissue
topic fascia
hyaluronan
vesicles
endocannabinoid
agonist
antagonist
url https://www.mdpi.com/1422-0067/21/8/2936
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