Osteoclast-derived exosomes inhibit osteogenic differentiation through Wnt/β-catenin signaling pathway in simulated microgravity model. (January 2019)

• Record Type: Journal Article
• Authors: Huyan, Ting; Du, Yongyong; Dong, Dandan; Li, Qi; Zhang, Ruixue; Yang, Jiancheng; Yang, Zhouqi; Li, Jingbao; Shang, Peng
• Is Part Of: Acta astronautica. Volume 154(2019)
• Page Start: 140
• Page End: 152
• Publication Date: 2019-01
• Subjects: Exosomes -- Microgravity -- Bone remodeling -- Osteoclasts -- Osteoblasts; Astronautics -- Periodicals; Outer space -- Exploration -- Periodicals; Astronautics; Periodicals; 629.405
• DOI: 10.1016/j.actaastro.2018.08.044
• Languages: English
• ISSNs: 0094-5765

Abstract

Abstract: In the microgravity environment of space, astronauts undergo osteoporosis due to an imbalance in bone remodeling. Recent studies have shown that exosomes derived from osteoclasts could mediate cell-to-cell communication in bone remodeling. However, the role of osteoclast-derived exosomes in bone remodeling in microgravity remains a mystery. Our objective is to investigate the cellular processes modulated by exosomes from RAW264.7 cell-derived osteoclasts and the underlying mechanism of action for the exosomes-mediated osteogenesis of osteoblast-like MC3T3-E1 cells in simulated microgravity. We took advantage of the random positioning machine (RPM) to simulate microgravity for the model and investigated the role of exosomes from RAW264.7 cell-derived osteoclasts in osteoclast-osteoblast communication. The results showed that this type of mature osteoclast-derived exosomes (OC-Exos) in the RPM evidently inhibited the cellular proliferation of osteoblasts via inducing cellular apoptosis and altering their cell cycle distribution. Alkaline phosphatase and mineralization activity of MC3T3-E1 cells were significantly lower after treatment with OC-Exos from RPM and mRNA expression of osteoblast-specific genes were down-regulated. Further study confirmed that OC-Exos in RPM obstructed the differentiation of MC3T3-E1 cells by interfering with Wnt/β-catenin signaling pathway. Together, these observations demonstrated that OC-Exos played an essential role in the regulation of bone remodeling in the microgravity environment. These results shed light on a novel pathway of cross-talk between osteoclasts and osteoblasts, which will be helpful to explain the possible mechanisms underlying osteoporosis in microgravity. Graphical abstract: Highlights: Simulated microgravity (SMG) elevated osteoclastogenesis of RAW 264.7 cells. Osteoclast-derived exosomes (OC-Exos) in SMG inhibited proliferation of osteoblast. OC-Exos in SMG promoted apoptosis of MC3T3-E1 cells. OC-Exos in SMG altered cell cycle distribution of MC3T3-E1 cells. OC-Exos in SMG suppressed Wnt/β-catenin signaling pathway in MC3T3-E1 cells.