Exploring the impact of osteoprotegerin on osteoclast and precursor fusion: Mechanisms and modulation by ATP

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation Pub Date : 2024-06-13 DOI:10.1016/j.diff.2024.100789

Yunwen Peng , Hongyan Zhao , Sinan Hu , Yonggang Ma , Tao Han , Chuang Meng , Xishuai Tong , Hui Zou , Zongping Liu , Ruilong Song

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引用次数: 0

Abstract

Osteoclast (OC) differentiation, vital for bone resorption, depends on osteoclast and precursor fusion. Osteoprotegerin (OPG) inhibits osteoclast differentiation. OPG's influence on fusion and mechanisms is unclear. Osteoclasts and precursors were treated with OPG alone or with ATP. OPG significantly reduced OC number, area and motility and ATP mitigated OPG's inhibition. However, OPG hardly affected the motility of precusors. OPG downregulated fusion-related molecules (CD44, CD47, DC-STAMP, ATP6V0D2) in osteoclasts, reducing only CD47 in precursors. OPG reduced Connexin43 phosphorylated forms (P1 and P2) in osteoclasts, affecting only P2 in precursors. OPG disrupted subcellular localization of CD44, CD47, DC-STAMP, ATP6V0D2, and Connexin43 in both cell types. Findings underscore OPG's multifaceted impact, inhibiting multinucleated osteoclast and mononuclear precursor fusion through distinct molecular mechanisms. Notably, ATP mitigates OPG's inhibitory effect, suggesting a potential regulatory role for the ATP signaling pathway. This study enhances understanding of intricate processes in osteoclast differentiation and fusion, offering insights into potential therapeutic targets for abnormal bone metabolism.

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探索骨蛋白激酶对破骨细胞和前体融合的影响：机制及 ATP 的调节作用

破骨细胞（OC）的分化对骨吸收至关重要，它取决于破骨细胞和前体的融合。破骨细胞蛋白（OPG）会抑制破骨细胞的分化。OPG 对融合的影响和机制尚不清楚。破骨细胞和前体用 OPG 单独或与 ATP 一起处理。OPG 能明显减少破骨细胞的数量、面积和运动能力，而 ATP 能减轻 OPG 的抑制作用。然而，OPG 几乎不影响前体的运动。OPG 下调了破骨细胞中的融合相关分子（CD44、CD47、DC-STAMP、ATP6V0D2），只减少了前体中的 CD47。OPG 减少了破骨细胞中的 Connexin43 磷酸化形式（P1 和 P2），只影响了前体中的 P2。OPG 破坏了两种细胞类型中 CD44、CD47、DC-STAMP、ATP6V0D2 和 Connexin43 的亚细胞定位。研究结果强调了 OPG 的多方面影响，它通过不同的分子机制抑制多核破骨细胞和单核前体融合。值得注意的是，ATP 可减轻 OPG 的抑制作用，这表明 ATP 信号通路具有潜在的调节作用。这项研究加深了人们对破骨细胞分化和融合的复杂过程的了解，为异常骨代谢的潜在治疗靶点提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Differentiation 生物-发育生物学

CiteScore

4.10

自引率

3.40%

发文量

审稿时长

51 days

期刊介绍： Differentiation is a multidisciplinary journal dealing with topics relating to cell differentiation, development, cellular structure and function, and cancer. Differentiation of eukaryotes at the molecular level and the use of transgenic and targeted mutagenesis approaches to problems of differentiation are of particular interest to the journal. The journal will publish full-length articles containing original work in any of these areas. We will also publish reviews and commentaries on topics of current interest. The principal subject areas the journal covers are: • embryonic patterning and organogenesis • human development and congenital malformation • mechanisms of cell lineage commitment • tissue homeostasis and oncogenic transformation • establishment of cellular polarity • stem cell differentiation • cell reprogramming mechanisms • stability of the differentiated state • cell and tissue interactions in vivo and in vitro • signal transduction pathways in development and differentiation • carcinogenesis and cancer • mechanisms involved in cell growth and division especially relating to cancer • differentiation in regeneration and ageing • therapeutic applications of differentiation processes.