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Space microgravity drives transdifferentiation of human bone marrow‐derived mesenchymal stem cells from osteogenesis to adipogenesis
Author(s) -
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
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700208rr
Subject(s) - runx2 , adipogenesis , mesenchymal stem cell , microbiology and biotechnology , bone morphogenetic protein 2 , stem cell , chemistry , transdifferentiation , cellular differentiation , biology , transcription factor , biochemistry , gene , in vitro
Bone 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 mi‐crogravity, 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 β (CEBPB) , and peroxisome proliferator‐activated receptor‐γ (PPARG). In the analysis of signaling pathways specific for osteogenesis, we found that the expression and activity of RUNX2 was inhibited, expression of bone morpho‐genetic 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. FASEB J . 32, 4444–4458 (2018). www.fasebj.org