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

Tang, Donge1,2,3,4; Liu, Xiaohui1,2; Chen, Kezhi1,2; Li, Zhipeng1,2; Dai, Yong3,4; Xu, Jiake5; Zhang, Huan-Tian1,2,6,7; Gao, Xuejuan1,2; Liu, Langxia1,2

2020-07-15

Aging-US   影响因子和分区

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 beta-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.

PCNA actin belt cytoplasm osteoclast differentiation

SCI

英语

其他

Natural Science Foundation of Guangdong Province[2019A1515010182][2018A030313544][2017A030313665] ; Guangzhou Science and Technology Project[201707010263][201707010493] ; National Natural Science Foundation of China[81602360] ; Macau Foundation for Development of Science and Technology[0029/2019/A]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:000549885700018

IMPACT JOURNALS LLC

Web of Science

1.Jinan Univ, Inst Life & Hlth Engn, Key Lab Funct Prot Res, Guangdong Higher Educ Inst, Guangzhou 510632, Peoples R China
2.Jinan Univ, Inst Life & Hlth Engn, MOE Key Lab Tumor Mol Biol, Guangzhou 510632, Peoples R China
3.Jinan Univ, Clin Med Coll 2, Dept Clin Med Res Ctr, Shenzhen 518020, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
5.Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia
6.Jinan Univ, Affiliated Hosp 1, Inst Orthoped Dis, Guangzhou, Guangdong, Peoples R China
7.Jinan Univ, Affiliated Hosp 1, Dept Bone & Joint Surg, Guangzhou, Guangdong, Peoples R 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.