文献类型：期刊文献

英文题名：FSTL1 promotes osteoclast differentiation and Accelerates periprosthetic osteolysis via PP2A Cα-Mediated activation of the JNK signaling pathway

作者：Li, Maoyuan[1,2];Wang, Liangliang[1];Lu, Feng[1,2];Li, Shishuo[1,3];Yu, Yunyuan[4];Hu, Huiqun[5,6];Yin, Guangrong[1];Xu, Chao[1];Liu, Yimin[1,2];Wang, Yuji[1,7,8]

第一作者：Li, Maoyuan

通信作者：Wang, YJ[1];Wang, YJ[2];Wang, YJ[3]

机构：[1]Nanjing Med Univ, Affiliated Hosp 3, Changzhou Peoples Hosp 2, Dept Orthoped, Changzhou 213003, Jiangsu, Peoples R China;[2]Nanjing Med Univ, Nanjing 210000, Peoples R China;[3]Dalian Med Univ, Grad Sch, Dalian 116044, Liaoning, Peoples R China;[4]Soochow Univ, Affiliated Hosp 3, Articular Orthopaed, Changzhou 213003, Peoples R China;[5]Zhejiang Canc Hosp, Dept Thorac Radiat Oncol, Hangzhou 310022, Peoples R China;[6]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Infect Dis, Hangzhou 310009, Peoples R China;[7]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[8]Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55905 USA

第一机构：Nanjing Med Univ, Affiliated Hosp 3, Changzhou Peoples Hosp 2, Dept Orthoped, Changzhou 213003, Jiangsu, Peoples R China

通信机构：[1]corresponding author), Nanjing Med Univ, Affiliated Hosp 3, Changzhou Peoples Hosp 2, Dept Orthoped, Changzhou 213003, Jiangsu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[3]corresponding author), Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55905 USA.|[10735]甘肃中医药大学;

年份：2025

卷号：242

外文期刊名：BIOCHEMICAL PHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-105019277907);WOS:【SCI-EXPANDED(收录号:WOS:001605475800001)】；

基金：Funding sources This study was supported by the Clinical Research Project of Changzhou Medical Center of Nanjing Medical University (CZKYCMCB202215) .

语种：英文

外文关键词：Periprosthetic osteolysis; FSTL1; Osteoclast differentiation; Ti nanoparticle; PP2A

摘要：Periprosthetic osteolysis (PPO) is a common cause of arthroplasty failure, characterized by chronic inflammation and osteoclast differentiation, ultimately necessitating revision surgery. Follistatin-like 1 (FSTL1) is a critical modulator of inflammation and has an important function in different inflammatory disorders, including osteoarthritis and rheumatoid arthritis. This research examines the function of FSTL1 in PPO and elucidates the underlying mechanisms. In human aseptic loosening periprosthetic interface membranes and titanium (Ti) nanoparticle-induced calvarial osteolysis models, FSTL1 expression was markedly elevated. The administration of recombinant FSTL1 (rFSTL1) to calvariae significantly exacerbated Ti nanoparticle-induced bone resorption at osteolytic sites and increased both osteoclastogenesis and pro-inflammatory factor expression. However, the knockdown of FSTL1 using adeno-associated virus (AAV) effectively mitigated calvarial osteolysis and decreased both osteoclastogenesis and pro-inflammatory factor expression. Mechanistically, FSTL1 facilitates osteoclast differentiation and bone resorption through the upregulation of protein phosphatase 2A C subunit alpha (PP2A C alpha) expression, which enhances the RANKL-induced activation of the JNK signaling pathway, thereby increasing the expression of downstream transcription factors cellular proto-oncogene Fos (c-Fos) and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Furthermore, FSTL1 intensifies the inflammatory response at osteolytic sites, also contributing to the progression of osteolysis. Our findings indicate that FSTL1 may represent a promising therapeutic target for the treatment of periprosthetic osteolysis.