ArticleJournal of cellular physiology2018
GSK-3β inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation.
Article in Journal of cellular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- Regenerative bone-targeted nanoparticles modulate osteoclast function.Nanoscale horizons · 2026Article
- Article
- Epigenetic factors associated with peri-implantitis: a review.Journal of Zhejiang University. Science. B · 2025Review
- Anti-osteoporotic effects and good biocompatibility of novel bioactive carbon quantum dotsiScience · 2025Article
- CombiningFrontiers in cell and developmental biology · 2025Article
- Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis.Frontiers in pharmacology · 2025Article
- Glycogen Synthase Kinase-3 Beta (GSK3β) as a Potential Drug Target in Regulating Osteoclastogenesis: An Updated Review on Current Evidence.Biomolecules · 2024Review
- Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula.International journal of molecular sciences · 2024Article
- Titanium particles inhibit bone marrow mesenchymal stem cell osteogenic differentiation through the MAPK signaling pathway.FEBS open bio · 2023Article
- Wnt pathway in bone: knowledge structure and hot spots from 1993 to 2022.Frontiers in physiology · 2023Article
- Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling.Frontiers in immunology · 2022Article
- Increasing Odontoblast-like Differentiation from Dental Pulp Stem Cells through Increase of β-Catenin/p-GSK-3β Expression by Low-Frequency Electromagnetic Field.Biomedicines · 2021Article
- Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway.Journal of cellular and molecular medicine · 2021Article
- Bone Homeostasis and Gut Microbial-Dependent Signaling Pathways.Journal of microbiology and biotechnology · 2021Review
- Recent Progresses in the Treatment of Osteoporosis.Frontiers in pharmacology · 2021Review
- Development of an immunogenomic landscape for the competing endogenous RNAs network of peri-implantitis.BMC medical genetics · 2020Article
- Local Wnt3a treatment restores bone regeneration in large osseous defects after surgical debridement of osteomyelitis.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Mechanical instability induces osteoclast differentiation independent of the presence of a fibrous tissue interface and osteocyte apoptosis in a rat model for aseptic loosening.Acta orthopaedica · 2020Article
- The Effects of Biomaterial Implant Wear Debris on Osteoblasts.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Currently, there are no medications available to treat aseptic loosening of orthopedic implants. Using osteoprotegerin fusion protein (OPG-Fc), we previously blocked instability-induced osteoclast differentiation and peri-prosthetic osteolysis. Wnt/β-catenin signaling, which regulates OPG secretion from osteoblasts, also modulates the bone tissue response to mechanical loading. We hypothesized that activating Wnt/β-catenin signaling by inhibiting glycogen synthase kinase-3β (GSK-3β) would reduce instability-induced bone loss through regulation of both osteoblast and osteoclast differentiation. We examined effects of GSK-3β inhibition on regulation of RANKL and OPG in a rat model of mechanical instability-induced peri-implant osteolysis. The rats were treated daily with a GSK-3β inhibitor, AR28 (20 mg/kg bw), for up to 5 days. Bone tissue and blood serum were assessed by qRT-PCR, immunohistochemistry, and ELISA on days 3 and 5, and by micro-CT on day 5. After 3 days of treatment with AR28, mRNA levels of β-catenin, Runx2, Osterix, Col1α1, and ALP were increased leading to higher osteoblast numbers compared to vehicle-treated animals. BMP-2 and Wnt16 mRNA levels were downregulated by mechanical instability and this was rescued by GSK-3β inhibition. Osteoclast numbers were decreased significantly after 3 days of GSK-3β inhibition, which correlated with enhanced OPG mRNA expression. This was accompanied by decreased serum levels of TRAP5b on days 3 and 5. Treatment with AR28 upregulated osteoblast differentiation, while osteoclastogenesis was blunted, leading to increased bone mass by day 5. These data suggest that GSK-3β inactivation suppresses osteolysis through regulating both osteoblast and osteoclast differentiation in a rat model of instability-induced osteolysis.
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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.