Beyond resorption: osteoclasts as drivers of bone formation.

IF 4 Q2 CELL & TISSUE ENGINEERING
Qianfeng Xiang, Lei Li, Wei Ji, Debby Gawlitta, X Frank Walboomers, Jeroen J J P van den Beucken
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引用次数: 0

Abstract

Emerging evidence illustrates that osteoclasts (OCs) play diverse roles beyond bone resorption, contributing significantly to bone formation and regeneration. Despite this, OCs remain mysterious cells, with aspects of their lifespan-from origin, fusion, alterations in cellular characteristics, to functions-remaining incompletely understood. Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors (OCPs) derived from erythromyeloid progenitors (EMPs). These precursor cells subsequently fuse into OCs essential for normal bone development and repair. Postnatally, hematopoietic stem cells (HSCs) become the primary source of OCs, gradually replacing EMP-derived OCs and assuming functional roles in adulthood. The absence of OCs during bone development results in bone structure malformation, including abnormal bone marrow cavity formation and shorter long bones. Additionally, OCs are reported to have intimate interactions with blood vessels, influencing bone formation and repair through angiogenesis regulation. Upon biomaterial implantation, activation of the innate immune system ensues immediately. OCs, originating from macrophages, closely interact with the immune system. Furthermore, evidence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes. Nevertheless, achieving a pure OC culture remains challenging, and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials. We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process, providing guidance for researchers in identifying OCs both in vitro and in vivo. This review focuses on OC formation, characterization, and the roles of OCs beyond resorption in various bone pathophysiological processes. Finally, therapeutic strategies targeting OCs are discussed.

超越吸收:破骨细胞是骨形成的驱动力。
新出现的证据表明,破骨细胞(OCs)在骨吸收之外还发挥着多种作用,对骨形成和再生做出了重要贡献。尽管如此,破骨细胞仍然是一种神秘的细胞,人们对其生命周期的各个方面--从起源、融合、细胞特征的改变到功能--仍然知之甚少。最近的研究发现,胚胎破骨细胞的形成主要是由来自红细胞髓样祖细胞(EMPs)的破骨细胞前体细胞(OCPs)驱动的。这些前体细胞随后融合成对正常骨骼发育和修复至关重要的破骨细胞。出生后,造血干细胞(HSCs)成为 OCs 的主要来源,逐渐取代 EMP 衍生的 OCs,并在成年后发挥功能作用。在骨骼发育过程中,OCs 的缺失会导致骨骼结构畸形,包括骨髓腔形成异常和长骨变短。此外,据报道,OC 与血管有密切的相互作用,通过血管生成调节影响骨骼的形成和修复。生物材料植入后,先天性免疫系统会立即激活。源于巨噬细胞的 OC 与免疫系统密切相关。此外,材料诱导骨形成事件的证据表明,OCs 在这些新生骨形成过程中起着关键作用。然而,实现纯粹的 OC 培养仍然具有挑战性,而且由于成骨生物材料周围存在其他多核细胞,解释 OC 在体内的功能也面临困难。我们在此描述 OCP 的融合特征,总结 OC 融合过程中的可靠标记和形态变化,为研究人员在体外和体内识别 OC 提供指导。本综述侧重于 OC 的形成、表征以及 OC 在各种骨病理生理过程中除吸收外的作用。最后还讨论了针对 OCs 的治疗策略。
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
Cell Regeneration
Cell Regeneration Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
5.80
自引率
0.00%
发文量
42
审稿时长
35 days
期刊介绍: Cell Regeneration aims to provide a worldwide platform for researches on stem cells and regenerative biology to develop basic science and to foster its clinical translation in medicine. Cell Regeneration welcomes reports on novel discoveries, theories, methods, technologies, and products in the field of stem cells and regenerative research, the journal is interested, but not limited to the following topics: ◎ Embryonic stem cells ◎ Induced pluripotent stem cells ◎ Tissue-specific stem cells ◎ Tissue or organ regeneration ◎ Methodology ◎ Biomaterials and regeneration ◎ Clinical translation or application in medicine
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