ArticleScience advances2019
Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Effective Oral Delivery of Teriparatide Using Organoclay-Polymethacrylate Nanocomposites for Osteoporosis Therapy.Pharmaceutics · 2025Article
- CSRP2 promotes the glioblastoma mesenchymal phenotype via p130Cas-mediated NF-κB and MAPK pathways.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- HOXC11-mediated regulation of mitochondrial function modulates chemoresistance in colorectal cancer.BMC cancer · 2024Article
- Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.Nature biomedical engineering · 2023Article
- The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis.International journal of molecular sciences · 2023Review
- Creatine kinase brain-type regulates BCAR1 phosphorylation to facilitate DNA damage repair.iScience · 2023Article
- Mechanical stimulation controls osteoclast function through the regulation of CaCommunications biology · 2023Article
- Gravity's effect on biology.Frontiers in physiology · 2023Article
- Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization.International journal of molecular sciences · 2022Review
- Mechanisms of joint destruction in rheumatoid arthritis - immune cell-fibroblast-bone interactions.Nature reviews. Rheumatology · 2022Review
- Mechanical unloading aggravates bone destruction and tumor expansion in myeloma.Haematologica · 2022Article
- TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling.Bone research · 2021Article
- Gravitational Experimental Platform for Animal Models, a New Platform at ESA's Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models.International journal of molecular sciences · 2021Review
- Gravity sensing in plant and animal cells.NPJ microgravity · 2021Review
- Glucocorticoid counteracts cellular mechanoresponses by LINC01569-dependent glucocorticoid receptor-mediated mRNA decay.Science advances · 2021Article
- The regulation of RANKL by mechanical force.Journal of bone and mineral metabolism · 2021Review
- Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.
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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.