FAM96B negatively regulates FOSL1 to modulate the osteogenic differentiation and regeneration of periodontal ligament stem cells via ferroptosis

作者：Qianyi Qin, Haoqing Yang, Runzhi Guo, Yunfei Zheng, Yiping Huang, Luyuan Jin, Zhipeng Fan, Weiran Li · 发表于：Stem Cell Research & Therapy · 年份：2024 · DOI：10.1186/s13287-024-04083-7 · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、Bone and Dental Protein Studies、Oral microbiology and periodontitis research

BACKGROUND: Periodontal ligament stem cell (PDLSC)-based therapy is one of the methods to assist bone regeneration. Understanding the functional regulation of PDLSCs and the mechanisms involved is a crucial issue in bone regeneration. This study aimed to explore the roles of the family with sequence similarity 96 member B (FAM96B) in the functional regulation of PDLSCs. METHODS: To assess the osteogenic differentiation of PDLSCs, the alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative calcium analysis, and osteogenic marker detection were conducted. Transplantation PDLSCs under the dorsum of nude mice and into the rat calvarial defects were also performed. Then, FAM96B-overexpressed PDLSCs were used for RNA-sequencing and bioinformatic analysis. To evaluate the ferroptosis of PDLSCs, cytosolic reactive oxygen species (ROS), expression of glutathione peroxidase 4 (GPX4), mitochondrial morphology and functions including the mitochondrial ROS, mitochondria membrane potential, and mitochondrial respiration were detected. RESULTS: The osteogenic indicators ALP activity, level of mineralization, and osteocalcin expression were decreased in PDLSCs by FAM96B, which demonstrated that FAM96B inhibited the osteogenic differentiation of PDLSCs. FAM96B knockdown promoted the new bone formation of PDLSCs subcutaneously transplanted to the dorsum of nude mice. Then, related biological functions were detected by the RNA-sequencing and the ferroptosis was focused. F...