ArticleCell death and differentiation2018
TSC1 regulates osteoclast podosome organization and bone resorption through mTORC1 and Rac1/Cdc42.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- The IRE1-XBP1s Axis Drives Inflammatory Osteolysis by Regulating a 5-HT Dependent Endogenous Anti-Autophagy Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- UCHL1 enhancesHistology and histopathology · 2026Article
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- Mechanistic Insights into Kaempferol's Therapeutic Effects on Postmenopausal Osteoporosis: A Proteomic and Experimental Validation in Ovariectomized Rats.Combinatorial chemistry & high throughput screening · 2026Article
- Targeting chaperone-mediated autophagy to regulate osteoclast activity as a therapeutic strategy for osteoporosis.Materials today. Bio · 2025Article
- Topography-based implants for bone regeneration: Design, biological mechanism, and therapeutics.Materials today. Bio · 2025Review
- Epimedium Brevicornu and Curculigo orchioides inhibit osteoclast autophagy by degrading the level of miRNA-199 to regulate the mTOR signaling pathway.Journal of orthopaedic surgery and research · 2025Article
- Article
- PMAIP1 regulates autophagy in osteoblasts via the AMPK/mTOR pathway in osteoporosis.Human cell · 2024Article
- Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Reprogramming tumor-associated macrophages to outcompete endovascular endothelial progenitor cells and suppress tumor neoangiogenesis.Immunity · 2023Article
- Abr, a Rho-regulating protein, modulates osteoclastogenesis by enhancing lamellipodia formation by interacting with poly(ADP-ribose) glycohydrolase.Molecular biology reports · 2023Article
- Article
- PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis.Journal of clinical laboratory analysis · 2022Article
- The crosstalk between MYC and mTORC1 during osteoclastogenesis.Frontiers in cell and developmental biology · 2022Article
- Role of TSC1 in physiology and diseases.Molecular and cellular biochemistry · 2021Review
- Review
- 4-Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF-κB signaling pathway and reverses bone loss in ovariectomized mice.Experimental and therapeutic medicine · 2021Article
- STIM1 controls calcineurin/Akt/mTOR/NFATC2-mediated osteoclastogenesis induced by RANKL/M-CSF.Experimental and therapeutic medicine · 2020Article
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reorganization of the podosome into the sealing zone is crucial for osteoclasts (OCLs) to resorb bone, but the underlying mechanisms are unclear. Here, we show that tuberous sclerosis complex 1 (TSC1) functions centrally in OCLs to promote podosome organization and bone resorption through mechanistic target of rapamycin complex 1 (mTORC1) and the small GTPases Rac1/Cdc42. During osteoclastogenesis, enhanced expression of TSC1 downregulates mTORC1 activity. TSC1 deletion in OCLs reduced podosome belt formation in vitro and sealing zone formation in vivo, leading to bone resorption deficiency and osteopetrosis. Mechanistically, TSC1 promoted podosome superstructure assembly by releasing mTORC1-dependent negative feedback inhibition of Rac1/Cdc42. Rapamycin and active Rac1/Cdc42 restore podosome organization and bone resorption and alleviate osteopetrotic phenotypes in mutant mice. Our findings reveal an essential role of TSC1 signaling in the regulation of bone resorption. Targeting TSC1 represents a novel strategy to inhibit bone resorption and prevent bone loss-related diseases.
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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.