PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■前交叉韧带（ACL）损伤被认为是骨关节炎（OA）进展的危险因素。在这里，研究了TAF15在ACL损伤诱导的OA中的作用。
■通过白细胞介素-1β（IL-1β）刺激和ACL横断给药建立OA细胞模型和OA小鼠模型，分别。通过组织病理学分析病理改变。使用qRT-PCR评估mRNA和蛋白质表达，Westernblot和IHC。通过CCK8测定和TUNEL染色检查软骨细胞活力和凋亡，分别。通过RIP或ChIP测定法分析TAF15、BRD4和GREM1之间的相互作用。
■在OA中TAF15表达显著升高,其敲除抑制了IL-1β诱导的体内软骨细胞凋亡和ECM降解以及体外软骨病理变化。TAF15促进BRD4mRNA稳定性，BRD4过表达后，TAF15沉默对IL-1β诱导的软骨细胞凋亡和ECM降解的抑制作用被消除。BRD4通过与GREM1直接结合促进GREM1表达。此外,GREM1/NF-κB通路作为BRD4的下游通路，促进OA的进展。
■TAF15上调通过作用于BRD4/GREM1/NF-κB轴促进OA发育过程中软骨细胞凋亡和ECM降解，为开发新型OA治疗方法提供了理论依据。
■通过白细胞介素-1β（IL-1β）刺激和ACL横断给药建立OA细胞模型和OA小鼠模型，分别。通过组织病理学分析病理改变。使用qRT-PCR评估mRNA和蛋白质表达，Westernblot和IHC。通过CCK8测定和TUNEL染色检查软骨细胞活力和凋亡，分别。通过RIP或ChIP测定法分析TAF15、BRD4和GREM1之间的相互作用。
■在OA中TAF15表达显著升高,其敲除抑制了IL-1β诱导的体内软骨细胞凋亡和ECM降解以及体外软骨病理变化。TAF15促进BRD4mRNA稳定性，BRD4过表达后，TAF15沉默对IL-1β诱导的软骨细胞凋亡和ECM降解的抑制作用被消除。BRD4通过与GREM1直接结合促进GREM1表达。此外,GREM1/NF-κB通路作为BRD4的下游通路，促进OA的进展。
■TAF15上调通过作用于BRD4/GREM1/NF-κB轴促进OA发育过程中软骨细胞凋亡和ECM降解，为开发新型OA治疗方法提供了理论依据。
