Cargando…

Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects

The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations...

Descripción completa

Detalles Bibliográficos
Autores principales: Ko, Po-Yen, Hsu, Che-Chia, Chen, Shih-Yao, Kuo, Li-Chieh, Su, Wei-Ren, Jou, I-Ming, Su, Fong-Chin, Wu, Po-Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456262/
https://www.ncbi.nlm.nih.gov/pubmed/36077161
http://dx.doi.org/10.3390/ijms23179760
_version_ 1784785770915037184
author Ko, Po-Yen
Hsu, Che-Chia
Chen, Shih-Yao
Kuo, Li-Chieh
Su, Wei-Ren
Jou, I-Ming
Su, Fong-Chin
Wu, Po-Ting
author_facet Ko, Po-Yen
Hsu, Che-Chia
Chen, Shih-Yao
Kuo, Li-Chieh
Su, Wei-Ren
Jou, I-Ming
Su, Fong-Chin
Wu, Po-Ting
author_sort Ko, Po-Yen
collection PubMed
description The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1β stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1β, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1β stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents.
format Online
Article
Text
id pubmed-9456262
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94562622022-09-09 Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects Ko, Po-Yen Hsu, Che-Chia Chen, Shih-Yao Kuo, Li-Chieh Su, Wei-Ren Jou, I-Ming Su, Fong-Chin Wu, Po-Ting Int J Mol Sci Article The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1β stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1β, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1β stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents. MDPI 2022-08-28 /pmc/articles/PMC9456262/ /pubmed/36077161 http://dx.doi.org/10.3390/ijms23179760 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ko, Po-Yen
Hsu, Che-Chia
Chen, Shih-Yao
Kuo, Li-Chieh
Su, Wei-Ren
Jou, I-Ming
Su, Fong-Chin
Wu, Po-Ting
Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
title Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
title_full Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
title_fullStr Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
title_full_unstemmed Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
title_short Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
title_sort cross-linked hyaluronate and corticosteroid combination ameliorate the rat experimental tendinopathy through anti-senescent and -apoptotic effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456262/
https://www.ncbi.nlm.nih.gov/pubmed/36077161
http://dx.doi.org/10.3390/ijms23179760
work_keys_str_mv AT kopoyen crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT hsuchechia crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT chenshihyao crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT kuolichieh crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT suweiren crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT jouiming crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT sufongchin crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects
AT wupoting crosslinkedhyaluronateandcorticosteroidcombinationamelioratetheratexperimentaltendinopathythroughantisenescentandapoptoticeffects