B lymphocytes impair osteogenesis by inhibiting BMSC differentiation in osteoporosis

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2025-07-01 DOI:10.1016/j.imbio.2025.153094

Cong Peng , Qiao Yang , Linyu Li , Yufeng Li , Zhaoyang Ye , Kun Zhao , Yi Yi , Liang Wang

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Abstract

Background: B lymphocytes have been implicated in the inhibition of osteogenesis, but their role in osteoporosis (OP) remains unclear. This study investigates the association between B lymphocytes and impaired osteogenesis in OP patients and explores the underlying mechanisms. Methods and materials: A retrospective analysis of 93 patients with OP assessed the relationship between B lymphocyte counts, bone formation marker Procollagen type I N-terminal propeptide (P1NP), and bone mineral density (BMD). An ovariectomy-induced OP mouse model was established. B lymphocytes and bone marrow mesenchymal stem cells (BMSCs) were isolated and co-cultured to evaluate the impact of B lymphocytes on osteogenic differentiation. Transcriptomic profiling and qPCR were performed to identify key regulatory genes. Results: Clinically, B lymphocyte counts were significantly elevated in OP patients with impaired osteogenesis (P < 0.05). Receiver operating characteristic (ROC) analysis indicated diagnostic potential (AUC = 0.638, P < 0.05). In vitro, B lymphocytes reduced Alkaline phosphatase (ALP) activity, calcium deposition, and the expression of osteogenic markers (Osterix, Cbfa1) in BMSCs. Transcriptomic analysis identified 210 differentially expressed genes, among which four (Ccdc170, Extl1, Smpd3, and Thsd4) were validated as potential mediators of B cell-induced osteogenesis inhibition. Conclusion: B lymphocytes may impair osteogenesis in OP by suppressing BMSC differentiation. These findings highlight B lymphocytes as potential diagnostic markers and therapeutic targets in osteoporosis.

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B淋巴细胞通过抑制骨质疏松症患者骨髓间充质干细胞分化而影响成骨

背景：B淋巴细胞与骨生成的抑制有关，但其在骨质疏松症（OP）中的作用尚不清楚。本研究探讨B淋巴细胞与OP患者成骨受损之间的关系，并探讨其潜在机制。方法与材料：回顾性分析93例OP患者B淋巴细胞计数、骨形成标志物I型前胶原n端前肽（P1NP）与骨密度（BMD）的关系。建立卵巢切除致OP小鼠模型。将B淋巴细胞与骨髓间充质干细胞（BMSCs）分离并共培养，观察B淋巴细胞对成骨分化的影响。转录组学分析和qPCR鉴定关键调控基因。结果：临床上，OP成骨功能受损患者B淋巴细胞计数明显升高(P <；0.05)。受试者工作特征（ROC）分析显示诊断潜力(AUC = 0.638, P <；0.05)。在体外实验中，B淋巴细胞降低了骨髓间充质干细胞中碱性磷酸酶（ALP）活性、钙沉积和成骨标志物（Osterix、Cbfa1）的表达。转录组学分析鉴定出210个差异表达基因，其中4个（Ccdc170、Extl1、Smpd3和Thsd4）被证实为B细胞诱导的成骨抑制的潜在介质。结论：B淋巴细胞可能通过抑制骨髓间充质干细胞分化而影响骨成骨。这些发现强调B淋巴细胞是骨质疏松症的潜在诊断标志物和治疗靶点。

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.