| 1 | OTUB1 promotes osteoblastic bone formation through stabilizing FGFR2显示文摘Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying molecular mechanisms are not fully understood.Here,we show that the global and conditional osteoblast knockout of a deubiquitinase Otub1 result in low bone mass and poor bone strength due to defects in osteogenic differentiation and mineralization.Mechanistically,the stability of FGFR2,a crucial regulator of osteogenesis,is maintained by OTUB1.OTUB1 attenuates the E3 ligase SMURF1-mediated FGFR2 ubiquitination by inhibiting SMURF1’s E2 binding.In the absence of OTUB1,FGFR2 is ubiquitinated excessively by SMURF1,followed by lysosomal degradation.Consistently,adeno-associated virus serotype 9(AAV9)-delivered FGFR2 in knee joints rescued the bone mass loss in osteoblast-specific Otub1-deleted mice.Moreover,Otub1 mRNA level was significantly downregulated in bones from osteoporotic mice,and restoring OTUB1 levels through an AAV9-delivered system in ovariectomy-induced osteoporotic mice attenuated osteopenia.Taken together,our results suggest that OTUB1 positively regulates osteogenic differentiation and mineralization in bone homeostasis by controlling FGFR2 stability,which provides an optical therapeutic strategy to alleviate osteoporosis. | Qiong Zhu Yesheng Fu Chun-Ping Cui Yi Ding Zhikang Deng Chao Ning Fan Hu Chen Qiu Biyue Yu Xuemei Zhou Guan Yang Jiang Peng Weiguo Zou Cui Hua Liu Lingqiang Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，5： | 1 |
| 2 | Enrichment,expansion,and identification of stem-like cells from hepatic carcinoma HepG2 cells显示文摘Objective:To establish a method for enriching,culturing and identifying stem-like subpopulation from human hepatic carcinoma cells,and to explore its biological properties.Methods:HepG2cells were cultured in cancer stem cell(CSC)medium to form spheroids.The stem-like HepG2cells obtained from tumor spheroids were then expanded.Flow cytometry was used to detect the expression of CD90 and CD133on the surface of stem-like HepG2 cells.The in vitro colony forming ability and in vivo tumorigenicity were detected by clone formation assay and tumorigenesis assay.Results:HepG2cells could grow in suspension and form spheroids in CSC medium.The stem-like cells had the ability of self-renewal and proliferation.The expression of CD90and CD133on the surface of these stem-like cells were higher than those of parental HepG2cells(P<0.01).The colony formation ability of stem-like cells was higher than that of parental HepG2cells.When injected with 1×106 cells,stemlike cells could form tumors earlier than parental cells in nude mice.The stem-like cells’tumorigenesis rate was higher and the tumor size was larger than those of parental HepG2cells(P<0.01).Conclusion:The suspension sphere culture method could enrich stem-like cells from HepG2cells.The obtained stem-like cells possessed the properties of self-renewal in vitro and tumorigenicity in vivo. | Biyu Cui Yebing Pang Xuehui Zhang Jing Lan Xilei Li Manya Wu Xing Guo Rong Liang Yan Feng Xiaoling Luo | 2017 | 广西医科大学学报2017，34，1： | 0 |
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