Huaji Jiang , Yan Ding , Yongfu Wu , Yingchao Xie , Qinyu Tian , Cheng Yang , Yakui Liu , Xuemei Lin , Bin Song , Hebei He , Li Wan , Xinggui Tian
{"title":"Eupalinolide A通过TOLLIP介导的选择性自噬促进YAP降解，从而减轻创伤诱导的小鼠肌腱异位骨化。","authors":"Huaji Jiang , Yan Ding , Yongfu Wu , Yingchao Xie , Qinyu Tian , Cheng Yang , Yakui Liu , Xuemei Lin , Bin Song , Hebei He , Li Wan , Xinggui Tian","doi":"10.1016/j.phymed.2024.156163","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Inhibiting the aberrant osteogenic differentiation of tendon-derived stem cells (TDSCs) is an effective strategy for treating traumatic heterotopic ossification (HO) in tendons.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate whether eupalinolide A (EA) could prevent tendon HO progression by suppressing the osteogenic differentiation of TDSCs.</div></div><div><h3>Methods</h3><div>The effects of EA on osteogenic differentiation and key signaling pathways in TDSCs were examined <em>in vitro</em> to assess its therapeutic potential and elucidate the underlying molecular mechanisms. Furthermore, the therapeutic efficacy of EA was evaluated in a mouse model of trauma-induced tendon HO <em>via</em> local injection therapy.</div></div><div><h3>Results</h3><div>EA significantly inhibited the osteogenic differentiation of TDSCs by targeting YAP <em>in vitro</em>. Specifically, EA facilitated the recruitment of E3 ubiquitin ligase HECW1, which mediated K27-linked polyubiquitination of YAP, leading to its degradation <em>via</em> the TOLLIP-mediated selective autophagy pathway. <em>In vivo,</em> EA mitigated trauma-induced tendon HO by inhibiting the YAP pathway.</div></div><div><h3>Conclusions</h3><div>EA could be a potential therapeutic agent for treating traumatic tendon HO. The therapeutic target HECW1 involved in YAP degradation <em>via</em> autophagy presents a new therapeutic avenue to attenuate the progression of traumatic tendon HO.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"Article 156163"},"PeriodicalIF":6.7000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Eupalinolide A attenuates trauma-induced heterotopic ossification of tendon in mice by promoting YAP degradation through TOLLIP-mediated selective autophagy\",\"authors\":\"Huaji Jiang , Yan Ding , Yongfu Wu , Yingchao Xie , Qinyu Tian , Cheng Yang , Yakui Liu , Xuemei Lin , Bin Song , Hebei He , Li Wan , Xinggui Tian\",\"doi\":\"10.1016/j.phymed.2024.156163\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Inhibiting the aberrant osteogenic differentiation of tendon-derived stem cells (TDSCs) is an effective strategy for treating traumatic heterotopic ossification (HO) in tendons.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate whether eupalinolide A (EA) could prevent tendon HO progression by suppressing the osteogenic differentiation of TDSCs.</div></div><div><h3>Methods</h3><div>The effects of EA on osteogenic differentiation and key signaling pathways in TDSCs were examined <em>in vitro</em> to assess its therapeutic potential and elucidate the underlying molecular mechanisms. Furthermore, the therapeutic efficacy of EA was evaluated in a mouse model of trauma-induced tendon HO <em>via</em> local injection therapy.</div></div><div><h3>Results</h3><div>EA significantly inhibited the osteogenic differentiation of TDSCs by targeting YAP <em>in vitro</em>. Specifically, EA facilitated the recruitment of E3 ubiquitin ligase HECW1, which mediated K27-linked polyubiquitination of YAP, leading to its degradation <em>via</em> the TOLLIP-mediated selective autophagy pathway. <em>In vivo,</em> EA mitigated trauma-induced tendon HO by inhibiting the YAP pathway.</div></div><div><h3>Conclusions</h3><div>EA could be a potential therapeutic agent for treating traumatic tendon HO. The therapeutic target HECW1 involved in YAP degradation <em>via</em> autophagy presents a new therapeutic avenue to attenuate the progression of traumatic tendon HO.</div></div>\",\"PeriodicalId\":20212,\"journal\":{\"name\":\"Phytomedicine\",\"volume\":\"135 \",\"pages\":\"Article 156163\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2024-10-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0944711324008201\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711324008201","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Eupalinolide A attenuates trauma-induced heterotopic ossification of tendon in mice by promoting YAP degradation through TOLLIP-mediated selective autophagy
Background
Inhibiting the aberrant osteogenic differentiation of tendon-derived stem cells (TDSCs) is an effective strategy for treating traumatic heterotopic ossification (HO) in tendons.
Purpose
This study aimed to investigate whether eupalinolide A (EA) could prevent tendon HO progression by suppressing the osteogenic differentiation of TDSCs.
Methods
The effects of EA on osteogenic differentiation and key signaling pathways in TDSCs were examined in vitro to assess its therapeutic potential and elucidate the underlying molecular mechanisms. Furthermore, the therapeutic efficacy of EA was evaluated in a mouse model of trauma-induced tendon HO via local injection therapy.
Results
EA significantly inhibited the osteogenic differentiation of TDSCs by targeting YAP in vitro. Specifically, EA facilitated the recruitment of E3 ubiquitin ligase HECW1, which mediated K27-linked polyubiquitination of YAP, leading to its degradation via the TOLLIP-mediated selective autophagy pathway. In vivo, EA mitigated trauma-induced tendon HO by inhibiting the YAP pathway.
Conclusions
EA could be a potential therapeutic agent for treating traumatic tendon HO. The therapeutic target HECW1 involved in YAP degradation via autophagy presents a new therapeutic avenue to attenuate the progression of traumatic tendon HO.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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