Deciphering B Cell Heterogeneity and Pathogenic Mechanisms in Osteoporosis Through Single-Cell RNA Sequencing.

Background: Osteoporosis is characterized by reduced bone mineral density and disrupted bone microstructure, leading to an increased risk of fractures. This study aimed to investigate the role of B cell subpopulations in osteoporosis and their effects on bone metabolism using single-cell RNA sequencing. Methods: Single-cell RNA sequencing data from primary human femoral head tissue cells of three osteoporosis patients and one non-osteoporosis patient were obtained from the GEO dataset (GSE169396). Data preprocessing, integration, dimensionality reduction, clustering, and annotation were conducted using the Seurat package in R. Enrichment analysis, cell trajectory analysis, and intercellular communication analysis were then applied to investigate the role of B cells and the signaling pathways within B cell subpopulations in osteoporosis. Results: We identified six distinct B cell subpopulations, and further analysis revealed a higher proportion of precursor B cells in osteoporosis patients compared to the normal group. Functional studies indicated that B cells contribute to the progression of osteoporosis through inflammatory activation and the unfolded protein response. Cell communication analysis among these B cell subpopulations demonstrated markedly enhanced intercellular signaling in osteoporosis patients relative to the normal group. Notably, two critical signaling pathways, MIF-(CD74+CXCR4) and LGALS9-CD45, were identified as potential key regulators driving the progression of osteoporosis. Conclusion: This study underscores the heterogeneity and functions of B cells in osteoporosis, highlighting two signaling pathways implicated in disease progression. These findings offer novel insights into osteoporosis pathogenesis and suggest potential therapeutic targets for its treatment.