New Insights Into Osteoclast Biology.
New Insights Into Osteoclast Biology.
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作者：
McDonald MM;Kim AS;Mulholland BS;Rauner M
破骨细胞是多核细胞，其特征在于其独特的吸收大量骨的能力。因此，它们经常是治疗干预的目标，以改善骨丢失。在成年生物体中，破骨细胞来源于造血干细胞，并在巨噬细胞集落刺激因子（M-CSF）和NF-κB配体受体激活剂（RANKL）的影响下在多步过程中分化为破骨细胞。从历史上看，破骨细胞的生命周期被定义为线性的，由此谱系定向的单核前体融合以产生多核的高度特化和局部化的骨吞噬细胞，然后在数周内发生凋亡。最近通过谱系追踪、单细胞RNA测序、联体共生和活体成像方法的进展挑战了这一教条，揭示了它们具有更长的寿命和循环和经历细胞再循环的能力。事实上，这些新的见解强调，在稳态条件下，破骨细胞凋亡的发生率非常低。更重要的是，随着我们重新审视破骨细胞的形成和命运，在骨病理学和再生中靶向破骨细胞生物学的新方法正在出现。这篇综述简要总结了破骨细胞的历史生命周期，并强调了通过先进的方法，这导致了破骨细胞生物学的范式转变的最新发现。这些研究结果进行了讨论，在现有的和新兴的骨靶向治疗，骨病理，破骨细胞和细胞之间的通信驻留在骨或在遥远的网站。版权所有© 2021作者。JBMR Plus由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
Osteoclasts are multinucleated cells that are characterized by their unique ability to resorb large quantities of bone. Therefore, they are frequently the target of therapeutic interventions to ameliorate bone loss. In an adult organism, osteoclasts derive from hematopoietic stem cells and differentiate into osteoclasts within a multistep process under the influence of macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL). Historically, the osteoclast life cycle has been defined as linear, whereby lineage‐committed mononuclear precursors fuse to generate multinucleated highly specialized and localized bone phagocytic cells, which then undergo apoptosis within weeks. Recent advances through lineage tracing, single cell RNA sequencing, parabiosis, and intravital imaging approaches have challenged this dogma, revealing they have greater longevity and the capacity to circulate and undergo cell recycling. Indeed, these new insights highlight that under homeostatic conditions very few incidences of osteoclast apoptosis occur. More importantly, as we revisit the formation and fate of the osteoclast, novel methods to target osteoclast biology in bone pathology and regeneration are emerging. This review briefly summarizes the historical life cycle of osteoclasts and highlights recent discoveries made through advanced methodologies, which have led to a paradigm shift in osteoclast biology. These findings are discussed in light of both existing and emerging bone targeted therapeutics, bone pathologies, and communication between osteoclasts and cells resident in bone or at distant sites. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.