Actin cytoskeleton mediates BMP2-Smad signaling via calponin 1 in preosteoblast under simulated microgravity

Xu, Hongjie; Wu, Feng; Zhang, Hongyu; Yang, Chao; Li, Kai; Wang, Hailong; Yang, Huai; Liu, Yue; Bai, Ding; Tan, Yingjun; Yuan, Ming; Li, Yinghui; Dai, Zhongquan

doi:10.1016/j.biochi.2017.04.015

Cited by 29 publications

(24 citation statements)

References 46 publications

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“…Furthermore, we observed phosphorylation of profilin-2 and de-phosphorylation of extracellular signal–regulated kinases (ERKs) 1/2 on thyroid cells exposed to microgravity [24,25] and recognized that genes mostly up- and down-regulated during a ten-day space mission coded for enzymes involved in posttranslational modifications (PTM) of target proteins [26]. The observations are in accordance with publications of other researchers [27,28]. Hence, it is probable that a protein’s activation status determined by PTM, such as phosphorylation, glycosylation, ubiquitination and others [29,30], is also important for the cellular behavior under µ g .…”

Section: Introductionsupporting

confidence: 88%

Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity

Bauer

Wehland

Infanger

et al. 2018

IJMS

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When monolayers of tissue cancer cells of various origins are exposed to real or simulated microgravity, many cells leave the monolayer and assemble to three-dimensional (3D) aggregates (spheroids). In order to define the cellular machinery leading to this change in growth behavior of FTC-133 human thyroid cancer cells and MCF-7 breast cancer cells, we recently performed proteome analyses on these cell lines and determined the proteins’ accumulation in monolayer cells grown under 1g-conditions as well as in the cells of spheroids assembled under simulated microgravity during three and 14 days, respectively. At that time, an influence of the increment or decrement of some of the more than 5000 proteins detected in each cell line was investigated. In this study, we focused on posttranslational modifications (PTMs) of proteins. For this purpose, we selected candidates from the list of the proteins detected in the two preceding proteome analyses, which showed significant accumulation in spheroid cells as compared to 1g monolayer cells. Then we searched for those PTMs of the selected proteins, which according to the literature have already been determined experimentally. Using the Semantic Protocol and RDF Query Language (SPARQL), various databases were examined. Most efficient was the search in the latest version of the dbPTM database. In total, we found 72 different classes of PTMs comprising mainly phosphorylation, glycosylation, ubiquitination and acetylation. Most interestingly, in 35 of the 69 proteins, N6 residues of lysine are modifiable.

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Section: Introductionsupporting

confidence: 88%

Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity

Bauer

Wehland

Infanger

et al. 2018

IJMS

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“…Bone cell morphology is significantly modified following exposure to microgravity when compared to control cells (Guignandon et al, 1995;Hughes-Fulford, 2003). To adapt to the new mechanical environment the bone cells have reduced transcription and translation of cytoskeletal and cytoskeletalassociated proteins (Xu et al, 2017;Mann et al, 2019), decreased focal adhesion formation, together resulting in the increased formation of osteoclast resorption pits (Nabavi et al, 2011). Furthermore, the actin cytoskeleton of osteoblasts subjected to 4 days of microgravity exposure completely collapsed (Hughes-Fulford, 2003), significantly impacting multiple downstream signaling pathways, most notably, the inhibition of bone morphogenic protein (BMP) signaling axis (Patel et al, 2007;Xu et al, 2017).…”

Section: Microgravity Impact Bone Cell Signaling Response and Cartilamentioning

confidence: 99%

Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease

Bradbury

Choi

et al. 2020

Front. Cell Dev. Biol.

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A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease.

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“…and Shi, Xie, et al (2017) found that microgravity generated by a random positioning machine (RPM) significantly inhibited the differentiation, maturation and mineralization of osteoblasts. Xu et al, 2017). Blocking the disappearance of the primary cilium using cytochalasin D (≥98%) effectively offset the suppression of osteoblastic differentiation.…”

Section: The Primary Cilium As a Coordinator In Signal Transductionmentioning

confidence: 99%

“…In spaceflight missions aboard the ISS, most of the astronauts experienced decreased BMD in the lumbar vertebrae and femurs (Collet et al, 1997). Bone loss during spaceflight has also been reproduced on the ground by microgravity-based research approaches, such as bed rest studies, hindlimb suspension models and clinostat devices (Grimm et al, 2016;Xu et al, 2017). However, the mechanisms of osteogenesis inhibition in microgravity, especially the initial sensors of microgravity, remain unclear.…”

Section: The Primary Cilium As a Coordinator In Signal Transductionmentioning

confidence: 99%

“…Microgravity induces changes in the cytoskeleton, including polymerization, depolymerization, and changes in the array and direction of microfilaments and microtubules, in various cells under conditions of simulated and real microgravity (Aleshcheva et al, 2015;Crawfordyoung, 2006;Vorselen, Roos, Mac Kintosh, Wuite, & van Loon, 2014;Xu et al, 2017). However, it is providential that there is an intrinsic connection between cytoskeletal changes and the primary cilium.…”

Section: The Primary Cilium As a Coordinator In Signal Transductionmentioning

confidence: 99%

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Novel functions of the primary cilium in bone disease and cancer

Shi

Zhang

et al. 2019

Cytoskeleton

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The primary cilium, a sensory organelle that emanates from the cell surface of most mammalian cell types during growth arrest, has attracted the attention of many researchers over the past decade. Recently, a large number of new findings have assigned novel functions and roles to the primary cilium in signal transduction and related diseases, which has greatly augmented the importance of the cilium in human health and development. Here, we review emerging evidence supporting the primary cilium as a sensory organelle in signal transduction in microgravity, electromagnetic field sensing, chemosensation and tumorigenesis. We also present an overview of signal transduction crosstalk associated with the primary cilium in bone disease and cancer, including primary cilium-related Ca 2+ signaling, parathyroid hormone signaling, cAMP signaling, BMP/Smad1/5/8 signaling and Wnt signaling. We anticipate that emerging discoveries about the function of the primary cilium will provide novel insight into the molecular mechanisms of stimulus sensation, signal transduction and pathogenesis. K E Y W O R D Sbone disease, cancer, cytoskeleton, primary cilium, signal transduction

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Actin cytoskeleton mediates BMP2-Smad signaling via calponin 1 in preosteoblast under simulated microgravity

Cited by 29 publications

References 46 publications

Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity

Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity

Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease

Novel functions of the primary cilium in bone disease and cancer

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