Division of Bone and Mineral Diseases, Musculoskeletal Research Center; and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA; email:
Shriners Hospitals for Children, St. Louis, Missouri, USA.
Annu Rev Pathol. 2023 Jan 24;18:257-281. doi: 10.1146/annurev-pathmechdis-031521-040919. Epub 2022 Oct 7.
Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that affect a significant portion of the population. Although therapies that effectively target osteoclasts have been developed, they are associated with sometimes severe side effects, and a fuller understanding of osteoclast biology may lead to more specific treatments. Along those lines, a rich body of work has defined essential signaling pathways required for osteoclast formation, function, and survival. Nonetheless, recent studies have cast new light on long-held views regarding the origin of these cells during development and homeostasis, their life span, and the cellular sources of factors that drive their production and activity during homeostasis and disease. In this review, we discuss these new findings in the context of existing work and highlight areas of ongoing and future investigation.
破骨细胞是具有独特的吸收骨基质能力的多核细胞。破骨细胞的过度产生或激活会导致骨骼病变,影响到相当一部分人群。虽然已经开发出了能够有效靶向破骨细胞的疗法,但这些疗法会产生有时很严重的副作用,而对破骨细胞生物学的更深入了解可能会带来更具针对性的治疗方法。基于这一点,大量的研究已经确定了破骨细胞形成、功能和存活所必需的信号通路。尽管如此,最近的研究还是对这些细胞在发育和稳态期间的起源、它们的寿命以及在稳态和疾病期间驱动其产生和活性的细胞来源的长期观点提出了新的看法。在这篇综述中,我们将结合现有工作讨论这些新发现,并强调正在进行和未来的研究领域。