TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression
Background: Anterior cruciate ligament (ACL) injury is recognized as a risk factor for osteoarthritis (OA) progression. Herein, the function of TAF15 in ACL injury-induced OA was investigated. Methods: OA cell model and OA mouse model were established by interleukin-1 beta (IL-1β) stimulation and AC...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320423000640 |
| _version_ | 1827630294611525632 |
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| author | Xiufan Du Ruomei Xin Xiaoyan Chen Guangji Wang Chunhang Huang Kai Zhou Shunli Zhang |
| author_facet | Xiufan Du Ruomei Xin Xiaoyan Chen Guangji Wang Chunhang Huang Kai Zhou Shunli Zhang |
| author_sort | Xiufan Du |
| collection | DOAJ |
| description | Background: Anterior cruciate ligament (ACL) injury is recognized as a risk factor for osteoarthritis (OA) progression. Herein, the function of TAF15 in ACL injury-induced OA was investigated. Methods: OA cell model and OA mouse model were established by interleukin-1 beta (IL-1β) stimulation and ACL transection administration, respectively. The pathological changes were analyzed by histopathology. The mRNA and protein expressions were assessed using qRT-PCR, Western blot and IHC. Chondrocyte viability and apoptosis were examined by CCK8 assay and TUNEL staining, respectively. The interactions between TAF15, BRD4 and GREM1 were analyzed by RIP or ChIP assay. Results: TAF15 expression was markedly elevated in OA, and its knockdown suppressed IL-1β-induced chondrocyte apoptosis and ECM degradation in vivo and cartilage pathological changes in vitro. TAF15 promoted BRD4 mRNA stability, and TAF15 silencing's repression on chondrocyte apoptosis and ECM degradation induced by IL-1β was abrogated following BRD4 overexpression. BRD4 promoted GREM1 expression by directly binding with GREM1. In addition, the GREM1/NF-κB pathway functioned as the downstream pathway of BRD4 in promoting OA progression. Conclusion: TAF15 upregulation facilitated chondrocyte apoptosis and ECM degradation during OA development by acting on the BRD4/GREM1/NF-κB axis, which provided a theoretical basis for the development of novel therapies for OA. |
| first_indexed | 2024-03-09T14:04:44Z |
| format | Article |
| id | doaj.art-581eb8b8579f48a7bb00ab6649dd1bb7 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-03-09T14:04:44Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-581eb8b8579f48a7bb00ab6649dd1bb72023-11-30T05:07:47ZengElsevierRegenerative Therapy2352-32042023-12-0124227236TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progressionXiufan Du0Ruomei Xin1Xiaoyan Chen2Guangji Wang3Chunhang Huang4Kai Zhou5Shunli Zhang6Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Department of Sports Medicine, Haikou, 570311, Hainan, PR ChinaDanzhou People's Hospital, Nursing Department, Danzhou, 571700, Hainan, PR ChinaHainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Department of Stomatology, Haikou, 570311, Hainan, PR ChinaHainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Department of Sports Medicine, Haikou, 570311, Hainan, PR ChinaHainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Department of Sports Medicine, Haikou, 570311, Hainan, PR ChinaHainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Department of Sports Medicine, Haikou, 570311, Hainan, PR ChinaThe Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, Hainan, PR China; Corresponding author. The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Av, Haikou, 570216, Hainan, PR China. Tel.:+86 0898 66809130.Background: Anterior cruciate ligament (ACL) injury is recognized as a risk factor for osteoarthritis (OA) progression. Herein, the function of TAF15 in ACL injury-induced OA was investigated. Methods: OA cell model and OA mouse model were established by interleukin-1 beta (IL-1β) stimulation and ACL transection administration, respectively. The pathological changes were analyzed by histopathology. The mRNA and protein expressions were assessed using qRT-PCR, Western blot and IHC. Chondrocyte viability and apoptosis were examined by CCK8 assay and TUNEL staining, respectively. The interactions between TAF15, BRD4 and GREM1 were analyzed by RIP or ChIP assay. Results: TAF15 expression was markedly elevated in OA, and its knockdown suppressed IL-1β-induced chondrocyte apoptosis and ECM degradation in vivo and cartilage pathological changes in vitro. TAF15 promoted BRD4 mRNA stability, and TAF15 silencing's repression on chondrocyte apoptosis and ECM degradation induced by IL-1β was abrogated following BRD4 overexpression. BRD4 promoted GREM1 expression by directly binding with GREM1. In addition, the GREM1/NF-κB pathway functioned as the downstream pathway of BRD4 in promoting OA progression. Conclusion: TAF15 upregulation facilitated chondrocyte apoptosis and ECM degradation during OA development by acting on the BRD4/GREM1/NF-κB axis, which provided a theoretical basis for the development of novel therapies for OA.http://www.sciencedirect.com/science/article/pii/S2352320423000640OsteoarthritisAnterior cruciate ligament injuryTAF15BRD4The gremlin-1-NF-κB pathway |
| spellingShingle | Xiufan Du Ruomei Xin Xiaoyan Chen Guangji Wang Chunhang Huang Kai Zhou Shunli Zhang TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression Regenerative Therapy Osteoarthritis Anterior cruciate ligament injury TAF15 BRD4 The gremlin-1-NF-κB pathway |
| title | TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression |
| title_full | TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression |
| title_fullStr | TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression |
| title_full_unstemmed | TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression |
| title_short | TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression |
| title_sort | taf15 regulates the brd4 grem1 axis and activates the gremlin 1 nf κb pathway to promote oa progression |
| topic | Osteoarthritis Anterior cruciate ligament injury TAF15 BRD4 The gremlin-1-NF-κB pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2352320423000640 |
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