Musculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.
J Bone Miner Res. 2012 Jul;27(7):1439-47. doi: 10.1002/jbmr.1668.
Imbalances between bone resorption and formation lie at the root of disorders such as osteoporosis, Paget's disease of bone (PDB), and osteopetrosis. Recently, genetic and functional studies have implicated proteins involved in autophagic protein degradation as important mediators of bone cell function in normal physiology and in pathology. Autophagy is the conserved process whereby aggregated proteins, intracellular pathogens, and damaged organelles are degraded and recycled. This process is important both for normal cellular quality control and in response to environmental or internal stressors, particularly in terminally-differentiated cells. Autophagic structures can also act as hubs for the spatial organization of recycling and synthetic process in secretory cells. Alterations to autophagy (reduction, hyperactivation, or impairment) are associated with a number of disorders, including neurodegenerative diseases and cancers, and are now being implicated in maintenance of skeletal homoeostasis. Here, we introduce the topic of autophagy, describe the new findings that are starting to emerge from the bone field, and consider the therapeutic potential of modifying this pathway for the treatment of age-related bone disorders.
骨吸收和形成之间的失衡是骨质疏松症、佩吉特病（PDB）和骨硬化症等疾病的根源。最近，遗传和功能研究表明，参与自噬蛋白降解的蛋白质是正常生理和病理过程中骨细胞功能的重要介质。自噬是一种保守的过程，其中聚集的蛋白质、细胞内病原体和受损的细胞器被降解和回收。这个过程对于正常的细胞质量控制以及对环境或内部应激源的反应都很重要，特别是在终末分化的细胞中。自噬结构也可以作为分泌细胞中回收和合成过程的空间组织的枢纽。自噬的改变（减少、过度激活或损伤）与许多疾病有关，包括神经退行性疾病和癌症，现在也被认为与骨骼内稳态的维持有关。在这里，我们介绍自噬的主题，描述开始从骨领域出现的新发现，并考虑修饰这种途径治疗与年龄相关的骨骼疾病的治疗潜力。
