Department ofPathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Eur J Clin Invest. 2012 Dec;42(12):1332-41. doi: 10.1111/j.1365-2362.2012.02717.x. Epub 2012 Sep 23.
Bone remodelling maintains skeletal integrity by osteoclasts removing foci of damaged bone and osteoblasts replacing them with new bone. Diseases associated with increased bone resorption have increased remodelling often with inadequate bone formation and increased risk of fracture. New therapies are needed for these diseases to reduce resorption and increase formation.
The molecular mechanisms regulating osteoclast and osteoblast functions have become better understood in the past 20 years and have led to questioning of the long-held notion that osteoblastic cells have the dominant regulatory role over osteoclastic cells in bone remodelling. Here, we review current knowledge of how osteoclast formation and functions are regulated and describe how enhanced understanding of these has led to development of new drugs for the management of common bone diseases characterized by increased bone resorption.
Osteoclast formation and functions are regulated by cytokines, especially receptor activator of NF-κB ligand (RANKL) and macrophage-colony-stimulating factor (M-CSF). The differentiation, activity and lifecycle of osteoclasts are regulated in part by other cells that reside within the bone. These include osteoblasts, osteocytes and immune cells, which express these cytokines in response to most factors that promote bone resorption. RANKL and M-CSF activate numerous signalling pathways, which are potential targets for therapeutic intervention. Importantly, osteoclastic cells also function as positive and negative regulators of osteoblastic bone formation.
There are multiple targets within osteoclasts for pharmacologic intervention to prevent bone loss in osteoporosis and other resorptive bone diseases. However, novel therapies could also affect osteoblastic cell functions.
破骨细胞通过去除受损骨的焦点，成骨细胞用新骨取代它们，从而维持骨骼的完整性。与骨吸收增加相关的疾病通常具有骨形成不足和骨折风险增加的特征，因此需要新的治疗方法来减少骨吸收和增加骨形成。
在过去的 20 年中，调节破骨细胞和成骨细胞功能的分子机制已经得到了更好的理解，这使得人们对成骨细胞在骨重建中对破骨细胞具有主导调节作用的长期观点提出了质疑。在这里，我们回顾了目前对破骨细胞形成和功能的调节机制的认识，并描述了如何增强对这些机制的理解，从而开发出用于治疗以骨吸收增加为特征的常见骨骼疾病的新药。
破骨细胞的形成和功能受细胞因子的调节，特别是核因子κB 受体激活剂配体（RANKL）和巨噬细胞集落刺激因子（M-CSF）。破骨细胞的分化、活性和生命周期部分受到骨内其他细胞的调节。这些细胞包括成骨细胞、骨细胞和免疫细胞，它们会在大多数促进骨吸收的因素作用下表达这些细胞因子。RANKL 和 M-CSF 激活许多信号通路，这些信号通路是治疗干预的潜在靶点。重要的是，破骨细胞还可以作为成骨细胞骨形成的正调节和负调节因子。
在骨质疏松症和其他吸收性骨疾病中，有多个针对破骨细胞的药物干预靶点可以预防骨丢失。然而，新型疗法也可能影响成骨细胞的功能。
