Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Research Institute of Orthopedics, Zhejiang University, Hangzhou 310009, China.
Biomolecules. 2022 Oct 31;12(11):1602. doi: 10.3390/biom12111602.
Osteoporosis and osteoporotic fractures comprise a substantial health and socioeconomic burden. The leading cause of osteoporosis is an imbalance in bone formation and bone resorption caused by hyperactive osteoclasts. Therefore, a new strategy to suppress osteoclastogenesis is needed. Parkin is likely closely associated with bone metabolism, although its role in osteoclastogenesis is unclear. In this study, the Parkin protein inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, osteoclast-specific gene expression, F-actin ring formation, and bone resorption pit formation in vitro. Moreover, depletion of Parkin enhanced RANKL-induced osteoclast formation, osteoclast-specific gene expression, F-actin ring formation, and bone resorption pit formation. Reactive oxygen species (ROS) activity was suppressed, while autophagy was upregulated with the presence of the Parkin protein. ROS activity was upregulated and autophagy was decreased due to Parkin knockdown. In addition, intravenous administration of Parkin rescued ovariectomy-induced bone loss and reduced osteoclastogenesis in vivo. Collectively, Parkin has therapeutic potential for diseases associated with overactive osteoclasts.
骨质疏松症和骨质疏松性骨折给健康和社会经济带来了巨大的负担。骨质疏松症的主要原因是破骨细胞过度活跃导致的骨形成和骨吸收失衡。因此，需要一种新的抑制破骨细胞生成的策略。Parkin 可能与骨代谢密切相关，但其在破骨细胞生成中的作用尚不清楚。在这项研究中，Parkin 蛋白抑制了核因子-κB 配体（RANKL）诱导的体外破骨细胞形成、破骨细胞特异性基因表达、F-actin 环形成和骨吸收陷窝形成。此外，Parkin 耗竭增强了 RANKL 诱导的破骨细胞形成、破骨细胞特异性基因表达、F-actin 环形成和骨吸收陷窝形成。Parkin 蛋白存在时，活性氧（ROS）活性受到抑制，自噬上调。由于 Parkin 敲低，ROS 活性上调，自噬减少。此外，静脉给予 Parkin 可挽救去卵巢诱导的骨丢失，并减少体内的破骨细胞生成。综上所述，Parkin 具有治疗与过度活跃的破骨细胞相关疾病的潜力。
