Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation

作者：Zhi-Yuan Wei, Jian Zhou, Jie Shen, Dong Sun, Tianbao Gao, Qing Liu, Hongri Wu, Xiao Hua Wang, Shulin Wang, Shiyu Xiao, Chao Han, Di Yang, Hui Dong, Yuzhang Wu, Yi Zhang, Shuai Xu, Xian Wang, Jie Luo, Qijie Dai, Jun Zhu, Sien Lin, Fei Luo, Yi Tian, Zhao Xie · 发表于：Journal of Orthopaedic Translation · 年份：2024 · DOI：10.1016/j.jot.2024.06.010 · 被引用次数：10 · 研究领域：Bone Metabolism and Diseases、Bone health and osteoporosis research、Osteomyelitis and Bone Disorders Research

Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this cocult...