ArticleMolecular medicine (Cambridge, Mass.)2023
RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Genomic dissection of hoof and leg conformation in Swiss dairy cattle populations reveals polygenic architecture and a recessive HYAL1 nonsense variant affecting longevity in Holstein cattle.Genetics, selection, evolution : GSE · 2026Article
- Recapitulating Endochondral Ossification for Bone Repair: From Development to Engineering Strategy.Advanced healthcare materials · 2026Review
- Screening and validation of ZFYVE27 as a potential diagnostic biomarker for osteoporosis via integrative bioinformatics and machine learning approaches.Frontiers in immunology · 2026Article
- Multifunctional Peptide-Based Biohybrid for Targeted Reduction of Metastatic Breast Carcinoma-Associated Osteolysis.Journal of functional biomaterials · 2025Article
- Bone Microstructural Deterioration and miR-155/International journal of molecular sciences · 2025Article
- Bioinformatics analysis of Rho-signal transduction genes in postmenopausal osteoporosis and periodontitis.Scientific reports · 2025Article
- Evaluating regional heritability mapping methods for identifying QTLs in a wild population of Soay sheep.Heredity · 2025Article
- MAGI1 attenuates osteoarthritis by regulating osteoclast fusion in subchondral bone through the RhoA-ROCK1 signaling pathway.Journal of orthopaedic translation · 2025Article
- Specific macrophage RhoA targeting CRISPR-Cas9 for mitigating osteoclastogenesis-induced joint damage in inflammatory arthritis.Cell reports. Medicine · 2025Article
- The potential link between the development of Alzheimer's disease and osteoporosis.Biogerontology · 2025Review
- Mechanisms of isorhamnetin inhibition of osteoclast differentiation: insights from molecular dynamics simulations andFrontiers in pharmacology · 2025Article
- Isonardosinone suppresses osteoclastogenesis through TRAF2/TRAF6-mediated disruption of calcium signaling and coordinate inhibition of MAPK/NF-κB pathways.BBA advances · 2025Article
- Review
- Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells.International journal of molecular sciences · 2024Article
- Role of O-linked N-acetylglucosamine protein modification in oxidative stress-induced autophagy: a novel target for bone remodeling.Cell communication and signaling : CCS · 2024Review
- In Vitro Cell Culture Model for Osteoclast Activation during Estrogen Withdrawal.International journal of molecular sciences · 2024Article
- Effects of Improper Mechanical Force on the Production of Sonic Hedgehog, RANKL, and IL-6 in Human Periodontal Ligament Cells In Vitro.Dentistry journal · 2024Article
- Bone resorption by osteoclasts involves fine tuning of RHOA activity by its microtubule-associated exchange factor GEF-H1.Frontiers in physiology · 2024Article
- The Role of TAM Receptors in Bone.International journal of molecular sciences · 2023Review
- Correction: RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling.Molecular medicine (Cambridge, Mass.) · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe cytoskeletal architecture of osteoclasts (OCs) and bone resorption activity must be appropriately controlled for proper bone remodeling, which is associated with osteoporosis. The RhoA protein of GTPase plays a regulatory role in cytoskeletal components and contributes to osteoclast adhesion, podosome positioning, and differentiation. Although osteoclast investigations have traditionally been performed by in vitro analysis, however, the results have been inconsistent, and the significance of RhoA in bone physiology and pathology is still unknown.
methodsWe generated RhoA knockout mice by specifically deleting RhoA in the osteoclast lineage to understand more about RhoA's involvement in bone remodeling. The function of RhoA in osteoclast differentiation and bone resorption and the mechanisms were assessed using bone marrow macrophages (BMMs) in vitro. The ovariectomized (OVX) mouse model was adopted to examine the pathological effect of RhoA in bone loss.
resultsConditional deletion of RhoA in the osteoclast lineage causes a severe osteopetrosis phenotype, which is attributable to a bone resorption suppression. Further mechanistic studies suggest that RhoA deficiency suppresses Akt-mTOR-NFATc1 signaling during osteoclast differentiation. Additionally, RhoA activation is consistently related to the significant enhancement the osteoclast activity, which culminates in the development of an osteoporotic bone phenotype. Furthermore, in mice, the absence of RhoA in osteoclast precursors prevented occurring OVX-induced bone loss.
conclusionRhoA promoted osteoclast development via the Akt-mTOR-NFATc1 signaling pathway, resulting a osteoporosis phenotype, and that manipulating RhoA activity might be a therapeutic strategy for osteoporotic bone loss.
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