Compromised anti-osteoclastogenic and immunomodulatory functions of regulatory B cells (Bregs) aggravate inflammatory bone loss in post-menopausal osteoporosis

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-01-16 DOI:10.1016/j.bbadis.2025.167675

Leena Sapra , Chaman Saini , Pradyumna Kumar Mishra , Bhavuk Garg , Manish Gupta , Rupesh K. Srivastava

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引用次数: 0

Abstract

Regulatory-B-cells (Bregs) modulate immune-homeostasis. Variations in the number and function of Bregs have been associated with various immune-related ailments, highlighting the importance of Bregs under inflammatory-conditions. Previously, we discovered the anti-osteoclastogenic-potential of Bregs. However, the crucial role of Bregs in the onset and progression of post-menopausal osteoporosis (PMO) has never been explored. Interestingly, our temporal-kinetic study demonstrated that Bregs have a compromised dynamics and functionality which further contributes to inception and the progression of the inflammatory bone loss condition in the PMO. Our ex-vivo findings further elucidate a significant reduction in the immunomodulatory and anti-osteoclastogenic functions of Bregs under the estrogen deficient post-menopausal osteoporotic conditions. The current study for the first time reports the crucial role of dysregulated-Bregs (both functionally and numerically), in the development of PMO. Our findings thereby provide a novel concept for immuno-therapeutically targeting “Bregs”, for effective management and treatment of post-menopausal osteoporosis in the long run.

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调节B细胞（Bregs）的抗破骨细胞和免疫调节功能受损加重了绝经后骨质疏松症的炎症性骨质流失。

调节性b细胞（Bregs）调节免疫稳态。Bregs数量和功能的变化与各种免疫相关疾病有关，这突出了Bregs在炎症条件下的重要性。在此之前，我们发现了Bregs的抗破骨细胞潜能。然而，Bregs在绝经后骨质疏松症（PMO）发生和发展中的关键作用从未被探索过。有趣的是，我们的时间动力学研究表明，Bregs具有受损的动力学和功能，这进一步促进了PMO炎症性骨质流失状况的开始和进展。我们的离体研究结果进一步阐明，在雌激素缺乏的绝经后骨质疏松症条件下，Bregs的免疫调节和抗破骨细胞功能显著降低。目前的研究首次报道了失调的bregs（功能上和数值上）在PMO发展中的关键作用。因此，我们的研究结果为免疫治疗靶向“Bregs”提供了一个新的概念，从长远来看，可以有效地管理和治疗绝经后骨质疏松症。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.