Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation

Tang，Donge1,2; Liu，Xiaohui1; Chen，Kezhi1; Li，Zhipeng1; Dai，Yong2; Xu，Jiake3; Zhang，Huan Tian1,4; Gao，Xuejuan1; Liu，Langxia1

2020

10.18632/aging.103434

Aging-US   Impact Factor & Quartile

1945-4589

Osteoporosis (OP) is an age-related osteolytic disease and characterized by low bone mass and more prone to fracture due to active osteoclasts. Proliferating cell nuclear antigen (PCNA) has been long identified as a nuclear protein playing critical roles in the regulation of DNA replication and repair. Recently, a few studies have demonstrated the cytoplasmic localization of PCNA and its function associated with apoptosis in neutrophil and neuroblastoma cells. However, the involvement of PCNA, including the cytoplasmic PCNA, in the osteoclast differentiation remains unclear. In the present study, we show that PCNA is translocated from nucleus to cytoplasm during the RANKL-induced osteoclast differentiation, and localized in the actin belt of mature osteoclast. Knockdown of PCNA significantly affected the integrity of actin belt, the formation of multinucleated osteoclasts, the expression of osteoclast-specific genes, and the in vitro bone resorption. Interactomic study has revealed β-actin as the major interacting partner of the cytoplasmic PCNA, suggesting that cytoplasmic PCNA might play a critical role in the differentiation of osteoclast through regulation of actin-cytoskeleton remodeling. Taken together, our results demonstrate the critical role of cytoplasmic PCNA during the process of osteoclast differentiation, and provided a potential therapeutic target for treatment of osteoclast-related bone diseases.

Actin belt Cytoplasm Differentiation Osteoclast PCNA

English

Others

2-s2.0-85088495801

Scopus

1.Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology,Institute of Life and Health Engineering,Jinan University,Guangzhou,510632,China
2.Department of Clinical Medical Research Center,The Second Clinical Medical College of Jinan University,The First Affiliated Hospital Southern University of Science and Technology,Shenzhen People's Hospital,Shenzhen, Guangdong,518020,China
3.School of Pathology and Laboratory Medicine,University of Western Australia,Perth,6009,Australia
4.Institute of Orthopedic Diseases and Department of Bone and Joint Surgery,The First Affiliated Hospital,Jinan University,Guangzhou, Guangdong,510630,China

Tang，Donge,Liu，Xiaohui,Chen，Kezhi,et al. Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation[J]. Aging-US,2020,12(13):13297-13317.

Tang，Donge.,Liu，Xiaohui.,Chen，Kezhi.,Li，Zhipeng.,Dai，Yong.,...&Liu，Langxia.(2020).Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation.Aging-US,12(13),13297-13317.

Tang，Donge,et al."Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation".Aging-US 12.13(2020):13297-13317.