ArticleInternational journal of molecular sciences2022
Activation of Focal Adhesion Kinase Restores Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation via Wnt/Β-Catenin Pathway.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Research Progress on Mechanisms of Milk-Derived Functional Components in Regulating Bone Health and the Gut-Bone Axis.Nutrients · 2026Review
- ITGA1 promotes osteogenic differentiation of human periodontal ligament stem cells via FAK-mediated PI3K-Akt activation.Stem cell research & therapy · 2026Article
- A systematic review of microgravity on reproductive systems: Implications for space biology and human health.iScience · 2026Review
- Effects of microgravity mechanotransduction in bone tissue and cells: systematic review on primary cilium-dependent mechanisms.NPJ microgravity · 2026Article
- Aging and Altered Gravity: A Cellular Perspective.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers.FASEB bioAdvances · 2025Article
- Focal Adhesion Kinase Alleviates Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation by Activating Transcriptional Wnt/β-Catenin-BMP2-COL1 and Metabolic SIRT1-PGC-1α-CPT1A Pathways.International journal of molecular sciences · 2025Article
- Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions.International journal of molecular sciences · 2024Review
- Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration.Connective tissue research · 2024Review
- Sargassum polysaccharide attenuates osteoarthritis in rats and is associated with the up-regulation of the ITGβ1-PI3K-AKT signaling pathway.Journal of orthopaedic translation · 2024Article
- Modeled microgravity unravels the roles of mechanical forces in renal progenitor cell physiology.Stem cell research & therapy · 2024Article
- Article
- Microgravity and Musculoskeletal Health: What Strategies Should Be Used for a Great Challenge?Life (Basel, Switzerland) · 2023Review
- YAP Inhibition Alleviates Simulated Microgravity-Induced Mesenchymal Stem Cell Senescence via Targeting Mitochondrial Dysfunction.Antioxidants (Basel, Switzerland) · 2023Article
- Cellular and Molecular Signaling Meet the Space Environment.International journal of molecular sciences · 2023Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Simulated microgravity (SMG) inhibits osteoblast differentiation (OBD) and induces bone loss via the inhibition of the Wnt/β-catenin pathway. However, the mechanism by which SMG alters the Wnt/β-catenin pathway is unknown. We previously demonstrated that SMG altered the focal adhesion kinase (FAK)-regulated mTORC1, AMPK and ERK1/2 pathways, leading to the inhibition of tumor cell proliferation/metastasis and promoting cell apoptosis. To examine whether FAK similarly mediates SMG-dependent changes to Wnt/β-catenin in osteoblasts, we characterized mouse MC3T3-E1 cells cultured under clinostat-modeled SMG (µg) conditions. Compared to cells cultured under ground (1 g) conditions, SMG reduces focal adhesions, alters cytoskeleton structures, and down-regulates FAK, Wnt/β-catenin and Wnt/β-catenin-regulated molecules. Consequently, protein-2 (BMP2), type-1 collagen (COL1), alkaline-phosphatase activity and matrix mineralization are all inhibited. In the mouse hindlimb unloading (HU) model, SMG-affected tibial trabecular bone loss is significantly reduced, according to histological and micro-computed tomography analyses. Interestingly, the FAK activator, cytotoxic necrotizing factor-1 (CNF1), significantly suppresses all of the SMG-induced alterations in MC3T3-E1 cells and the HU model. Therefore, our data demonstrate the critical role of FAK in the SMG-induced inhibition of OBD and bone loss via the Wnt/β-catenin pathway, offering FAK signaling as a new therapeutic target not only for astronauts at risk of OBD inhibition and bone loss, but also osteoporotic patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.