Cargando…

Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model

Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (M...

Descripción completa

Detalles Bibliográficos
Autores principales: Ichiseki, Toru, Shimasaki, Miyako, Ueda, Yoshimichi, Ueda, Shusuke, Tsuchiya, Masanobu, Souma, Daisuke, Kaneuji, Ayumi, Kawahara, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796152/
https://www.ncbi.nlm.nih.gov/pubmed/29315262
http://dx.doi.org/10.3390/ijms19010203
_version_ 1783297445194629120
author Ichiseki, Toru
Shimasaki, Miyako
Ueda, Yoshimichi
Ueda, Shusuke
Tsuchiya, Masanobu
Souma, Daisuke
Kaneuji, Ayumi
Kawahara, Norio
author_facet Ichiseki, Toru
Shimasaki, Miyako
Ueda, Yoshimichi
Ueda, Shusuke
Tsuchiya, Masanobu
Souma, Daisuke
Kaneuji, Ayumi
Kawahara, Norio
author_sort Ichiseki, Toru
collection PubMed
description Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (MSC) to induce cartilage regeneration has been disappointing, MSC implantation is now being attempted using various surgical techniques. Meanwhile, prevention of osteoarthritis (OA) progression and pain control remain important components of the treatment of early-stage OA. We prepared a shoulder arthritis model by injecting monoiodoacetate (MIA) into a rat shoulder, and then investigated the intraarticular administration of MSC from the aspects of the cartilage protective effect associated with their anti-inflammatory property and inhibitory effect on central sensitization of pain. When MIA was administered in this rat shoulder arthritis model, anti-Calcitonin Gene Related Peptide (CGRP) was expressed in the joint and C5 spinal dorsal horn. Moreover, expression of A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), a marker of joint cartilage injury, was similarly elevated following MIA administration. When MSC were injected intraarticularly after MIA, the expression of CGRP in the spinal dorsal horn was significantly deceased, indicating suppression of the central sensitization of pain. The expression of ADAMTS 5 in joint cartilage was also significantly inhibited by MSC administration. In contrast, a significant increase in the expression of TNF-α stimulated gene/protein 6 (TSG-6), an anti-inflammatory and cartilage protective factor shown to be produced and secreted by MSC intraarticularly, was found to extend to the cartilage tissue following MSC administration. In this way, the intraarticular injection of MSC inhibited the central sensitization of pain and increased the expression of the anti-inflammatory and cartilage protective factor TSG-6. As the least invasive conservative strategies possible are desirable in the actual clinical setting, the intraarticular administration of MSC, which appears to be effective for the treatment of pain and cartilage protection in early-stage arthritis, may achieve these aims.
format Online
Article
Text
id pubmed-5796152
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-57961522018-02-09 Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model Ichiseki, Toru Shimasaki, Miyako Ueda, Yoshimichi Ueda, Shusuke Tsuchiya, Masanobu Souma, Daisuke Kaneuji, Ayumi Kawahara, Norio Int J Mol Sci Article Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (MSC) to induce cartilage regeneration has been disappointing, MSC implantation is now being attempted using various surgical techniques. Meanwhile, prevention of osteoarthritis (OA) progression and pain control remain important components of the treatment of early-stage OA. We prepared a shoulder arthritis model by injecting monoiodoacetate (MIA) into a rat shoulder, and then investigated the intraarticular administration of MSC from the aspects of the cartilage protective effect associated with their anti-inflammatory property and inhibitory effect on central sensitization of pain. When MIA was administered in this rat shoulder arthritis model, anti-Calcitonin Gene Related Peptide (CGRP) was expressed in the joint and C5 spinal dorsal horn. Moreover, expression of A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), a marker of joint cartilage injury, was similarly elevated following MIA administration. When MSC were injected intraarticularly after MIA, the expression of CGRP in the spinal dorsal horn was significantly deceased, indicating suppression of the central sensitization of pain. The expression of ADAMTS 5 in joint cartilage was also significantly inhibited by MSC administration. In contrast, a significant increase in the expression of TNF-α stimulated gene/protein 6 (TSG-6), an anti-inflammatory and cartilage protective factor shown to be produced and secreted by MSC intraarticularly, was found to extend to the cartilage tissue following MSC administration. In this way, the intraarticular injection of MSC inhibited the central sensitization of pain and increased the expression of the anti-inflammatory and cartilage protective factor TSG-6. As the least invasive conservative strategies possible are desirable in the actual clinical setting, the intraarticular administration of MSC, which appears to be effective for the treatment of pain and cartilage protection in early-stage arthritis, may achieve these aims. MDPI 2018-01-09 /pmc/articles/PMC5796152/ /pubmed/29315262 http://dx.doi.org/10.3390/ijms19010203 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ichiseki, Toru
Shimasaki, Miyako
Ueda, Yoshimichi
Ueda, Shusuke
Tsuchiya, Masanobu
Souma, Daisuke
Kaneuji, Ayumi
Kawahara, Norio
Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model
title Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model
title_full Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model
title_fullStr Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model
title_full_unstemmed Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model
title_short Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model
title_sort intraarticularly-injected mesenchymal stem cells stimulate anti-inflammatory molecules and inhibit pain related protein and chondrolytic enzymes in a monoiodoacetate-induced rat arthritis model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796152/
https://www.ncbi.nlm.nih.gov/pubmed/29315262
http://dx.doi.org/10.3390/ijms19010203
work_keys_str_mv AT ichisekitoru intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT shimasakimiyako intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT uedayoshimichi intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT uedashusuke intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT tsuchiyamasanobu intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT soumadaisuke intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT kaneujiayumi intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel
AT kawaharanorio intraarticularlyinjectedmesenchymalstemcellsstimulateantiinflammatorymoleculesandinhibitpainrelatedproteinandchondrolyticenzymesinamonoiodoacetateinducedratarthritismodel