ArticleBone2018
LARG GEF and ARHGAP18 orchestrate RhoA activity to control mesenchymal stem cell lineage.
Article in Bone, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Rgnef regulates bone mass through the activation of RhoA and Rac1.Experimental & molecular medicine · 2026Article
- Mechanism of ERK-mediated Rho Activation and Stress Fiber Assembly for Cell Migration.bioRxiv : the preprint server for biology · 2025Article
- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
- Loss of the auxiliary αJBMR plus · 2024Article
- Genomic and Reverse Translational Analysis Discloses a Role for Small GTPase RhoA Signaling in the Pathogenesis of Schizophrenia: Rho-Kinase as a Novel Drug Target.International journal of molecular sciences · 2023Review
- Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Gabapentin Disrupts Binding of Perlecan to the αBiomolecules · 2022Article
- The skeleton in a physical world.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Architectural control of mesenchymal stem cell phenotype through nuclear actin.Nucleus (Austin, Tex.) · 2022Article
- Apatinib Through Activating the RhoA/ROCK Signaling Pathway to Cause Dysfunction of Vascular Smooth Muscle Cells.Applied biochemistry and biotechnology · 2022Article
- ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Role of Rho GTPases in stem cell regulation.Biochemical Society transactions · 2021Review
- Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation.Scientific reports · 2021Article
- Review
- Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis.International journal of molecular sciences · 2021Article
- Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering.Frontiers in cell and developmental biology · 2021Review
- Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment.Frontiers in cell and developmental biology · 2021Article
- Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity.Bone research · 2020Article
- ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.Haematologica · 2020Article
- Gene regulation through dynamic actin control of nuclear structure.Experimental biology and medicine (Maywood, N.J.) · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partially through RhoA driven enhancement of cytoskeletal structure. To understand the basis of force-driven RhoA activation, we considered critical GEFs (activators) and GAPs (inactivators) on bone marrow MSC lineage fate. Knockdown of LARG accelerated adipogenesis and repressed basal RhoA activity. Importantly, mechanical activation of RhoA was almost entirely inhibited following LARG depletion, and the ability of strain to inhibit adipogenesis was impaired. Knockdown of ARHGAP18 increased basal RhoA activity and actin stress fiber formation, but did not enhance mechanical strain activation of RhoA. ARHGAP18 null MSCs exhibited suppressed adipogenesis assessed by Oil-Red-O staining and Western blot of adipogenic markers. Furthermore, ARHGAP18 knockdown enhanced osteogenic commitment, confirmed by alkaline phosphatase staining and qPCR of Sp7, Alpl, and Bglap genes. This suggests that ARHGAP18 conveys tonic inhibition of MSC cytoskeletal assembly, returning RhoA to an "off state" and affecting cell lineage in the static state. In contrast, LARG is recruited during dynamic mechanical strain, and is necessary for mechanical suppression of adipogenesis. In summary, mechanical activation of RhoA in mesenchymal progenitors is dependent on LARG, while ARHGAP18 limits RhoA delineated cytoskeletal structure in static cultures. Thus, on and off GTP exchangers work through RhoA to influence MSC fate and responses to static and dynamic physical factors in the microenvironment.
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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.