ArticleCell regeneration (London, England)2021
RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss.
Article in Cell regeneration (London, England), 2021. 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 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Actomyosin contractility is a potent suppressor of mesoderm induction by human pluripotent stem cells.The Journal of cell biology · 2026Article
- TRIM21 contributes to senile osteoporosis by shifting the osteoadipogenic balance toward adipogenesis in BMSCs.Science China. Life sciences · 2026Article
- A dual-action humanized DKK-1 antibody that activates the Wnt/β-catenin signaling pathway and inhibits the RANKL signaling pathway for osteoporosis therapy.Frontiers in immunology · 2026Article
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- RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer's Disease.Current issues in molecular biology · 2025Review
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- Biodegradable Zn-2Cu-0.5Zr alloy promotes the bone repair of senile osteoporotic fractures via the immune-modulation of macrophages.Bioactive materials · 2024Article
- Wnt/β-catenin signaling pathway as an important mediator in muscle and bone crosstalk: A systematic review.Journal of orthopaedic translation · 2024Review
- Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson's Disease and Aging.Biomedicines · 2024Review
- CHD4 and SMYD1 repress common transcriptional programs in the developing heart.Development (Cambridge, England) · 2024Article
- Correction: RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss.Cell regeneration (London, England) · 2024Article
- Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles.Frontiers in cell and developmental biology · 2024Article
- The Role of TAM Receptors in Bone.International journal of molecular sciences · 2023Review
- Cellular senescence in skeletal disease: mechanisms and treatment.Cellular & molecular biology letters · 2023Review
- Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA-ROCK-β-catenin signaling axis and static & dynamic dual roles.Molecular medicine (Cambridge, Mass.) · 2023Article
- Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1.Circulation research · 2023Article
- RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling.Molecular medicine (Cambridge, Mass.) · 2023Article
- Identifying Biomarkers for Osteogenic Potency Assay Development.Advances in experimental medicine and biology · 2023Article
- N-Cadherin adhesive ligation regulates mechanosensitive neural stem cell lineage commitment in 3D matrices.Biomaterials science · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis, whereas nuclear accumulation of β-catenin requires the activation of Rac1, a member of the Rho small GTPase family. The aim of the present study was to investigate the role of RhoA/Rho kinase (Rock)-mediated Wnt/β-catenin signaling in the regulation of aging-associated bone loss. We find that Lrp5/6-dependent and Lrp5/6-independent RhoA/Rock activation by Wnt3a activates Jak1/2 to directly phosphorylate Gsk3β at Tyr216, resulting in Gsk3β activation and subsequent β-catenin destabilization. In line with these molecular events, RhoA loss- or gain-of-function in mouse embryonic limb bud ectoderms interacts genetically with Dkk1 gain-of-function to rescue the severe limb truncation phenotypes or to phenocopy the deletion of β-catenin, respectively. Likewise, RhoA loss-of-function in pre-osteoblasts robustly increases bone formation while gain-of-function decreases it. Importantly, high RhoA/Rock activity closely correlates with Jak and Gsk3β activities but inversely correlates with β-catenin signaling activity in bone marrow mesenchymal stromal cells from elderly male humans and mice, whereas systemic inhibition of Rock therefore activates the β-catenin signaling to antagonize aging-associated bone loss. Taken together, these results identify RhoA/Rock-dependent Gsk3β activation and subsequent β-catenin destabilization as a hitherto uncharacterized mechanism controlling limb outgrowth and bone homeostasis.
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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.