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Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis
Zhang, Cui; Li, Liang; Jiang, Yuanda; Wang, Cuicui; Geng, Baoming; Wang, Yanqiu; Chen, Jianling; Liu, Fei; Qiu, Peng; Zhai, Guangjie; Chen, Ping; Quan, Renfu; Wang, Jinfu; Quan, RF (reprint author), Xiaoshan Tradit Chinese Med Hosp, Inst Orthoped, Hangzhou 311201, Zhejiang, Peoples R China.; Wang, JF (reprint author), Zhejiang Univ, Coll Life Sci, Zijingang Campus,866 Yuhangtang Rd, Hangzhou, Zhejiang, Peoples R China.
Department空间技术部
Source PublicationFASEB JOURNAL
2018
Volume32Issue:8Pages:4444-4458
ISSN0892-6638
Language英语
KeywordHmscs Signaling Pathway Sj-10 Satellite Rna-seq
AbstractBone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 satellite. The satellite returned to Earth after going through space experiments in orbit for 12 d, and cell samples were harvested and analyzed for differentiation potentials. The results showed that space microgravity inhibited osteogenic differentiation and resulted in adipogenic differentiation, even under osteogenic induction conditions. Under space microgravity, the expression of 10 genes specific for osteogenesis decreased, including collagen family members, alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2), whereas the expression of 4 genes specific for adipogenesis increased, including adipsin (CFD), leptin (LEP), CCAAT/enhancer binding protein (CEBPB), and peroxisome proliferator-activated receptor- (PPARG). In the analysis of signaling pathways specific for osteogenesis, we found that the expression and activity of RUNX2 was inhibited, expression of bone morphogenetic protein-2 (BMP2) and activity of SMAD1/5/9 were decreased, and activity of focal adhesion kinase (FAK) and ERK-1/2 declined significantly under space microgravity. These data indicate that space microgravity plays a dual role by decreasing RUNX2 expression and activity through the BMP2/SMAD and integrin/FAK/ERK pathways. In addition, we found that space microgravity increased p38 MAPK and protein kinase B (AKT) activities, which are important for the promotion of adipogenic differentiation of hMSCs. Space microgravity significantly decreased the expression of Tribbles homolog 3 (TRIB3), a repressor of adipogenic differentiation. Y15, a specific inhibitor of FAK activity, was used to inhibit the activity of FAK under normal gravity; Y15 decreased protein expression of TRIB3. Therefore, it appears that space microgravity decreased FAK activity and thereby reduced TRIB3 expression and derepressed AKT activity. Under space microgravity, the increase in p38 MAPK activity and the derepression of AKT activity seem to synchronously lead to the activation of the signaling pathway specifically promoting adipogenesis.Zhang, C., Li, L., Jiang, Y., Wang, C., Geng, B., Wang, Y., Chen, J., Liu, F., Qiu, P., Zhai, G., Chen, P., Quan, R., Wang, J. Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis.
Indexed BySCI
Document Type期刊论文
Identifierhttp://ir.nssc.ac.cn/handle/122/6393
Collection空间技术部
Corresponding AuthorQuan, RF (reprint author), Xiaoshan Tradit Chinese Med Hosp, Inst Orthoped, Hangzhou 311201, Zhejiang, Peoples R China.; Wang, JF (reprint author), Zhejiang Univ, Coll Life Sci, Zijingang Campus,866 Yuhangtang Rd, Hangzhou, Zhejiang, Peoples R China.
Recommended Citation
GB/T 7714
Zhang, Cui,Li, Liang,Jiang, Yuanda,et al. Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis[J]. FASEB JOURNAL,2018,32(8):4444-4458.
APA Zhang, Cui.,Li, Liang.,Jiang, Yuanda.,Wang, Cuicui.,Geng, Baoming.,...&Wang, JF .(2018).Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis.FASEB JOURNAL,32(8),4444-4458.
MLA Zhang, Cui,et al."Space microgravity drives transdifferentiation of human bone marrow-derived mesenchymal stem cells from osteogenesis to adipogenesis".FASEB JOURNAL 32.8(2018):4444-4458.
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