ArticleBone & joint research2021
LY3023414 inhibits both osteogenesis and osteoclastogenesis through the PI3K/Akt/GSK3 signalling pathway.
Article in Bone & joint research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Strategy based on liquid crystal elastomer active tensile to accelerate bone repair: Mechanistic analysis of LAMB1-ITGB4 mediated PI3K-AKT signaling.Materials today. Bio · 2026Article
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- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Discrimination of superficial lymph nodes using ultrasonography and tissue metabolomics coupled with machine learning.Frontiers in oncology · 2025Article
- PI3K/AKT signaling mediate collagen type 1-induced osteogenic differentiation of dental pulp stem cells via focal adhesion mechanism.Journal of applied oral science : revista FOB · 2025Article
- PTEN: an emerging target in rheumatoid arthritis?Cell communication and signaling : CCS · 2024Review
- Glycogen Synthase Kinase-3 Beta (GSK3β) as a Potential Drug Target in Regulating Osteoclastogenesis: An Updated Review on Current Evidence.Biomolecules · 2024Review
- Exploring the therapeutic potential of isoorientin in the treatment of osteoporosis: a study using network pharmacology and experimental validation.Molecular medicine (Cambridge, Mass.) · 2024Article
- Transcriptomic and proteomic strategies to reveal the mechanism of Gymnocypris przewalskii scale development.BMC genomics · 2024Article
- Bone repair and key signalling pathways for cell-based bone regenerative therapy: A review.Journal of Taibah University Medical Sciences · 2023Review
- mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.International journal of molecular sciences · 2023Review
- A Review of Signaling Transduction Mechanisms in Osteoclastogenesis Regulation by Autophagy, Inflammation, and Immunity.International journal of molecular sciences · 2022Review
- Osteocyte-specific dentin matrix protein 1 : the role of mineralization regulation in low-magnitude high-frequency vibration enhanced osteoporotic fracture healing.Bone & joint research · 2022Article
- Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis.Scientific reports · 2022Article
- Role of LINC01133 in Osteogenic Differentiation of Dental Pulp Stem Cells by Targeting miR-199b-5p.Oral health & preventive dentistry · 2022Article
- Duhuo Jisheng Decoction inhibits the activity of osteoclasts in osteonecrosis of the femoral head via regulation of the RELA/AKT1 axis.American journal of translational research · 2022Article
- Ferroptosis-related gene signatures in neuroblastoma associated with prognosis.Frontiers in cell and developmental biology · 2022Article
- Astragaloside positively regulated osteogenic differentiation of pre-osteoblast MC3T3-E1 through PI3K/Akt signaling pathway.Journal of orthopaedic surgery and research · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsLY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.
methodsThe function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.
resultsLY3023414 attenuated PI3K/protein kinase B (Akt)/GSK3-dependent activation of β-catenin and nuclear factor-activated T cell 1 (NFATc1) during osteogenesis and osteoclastogenesis, respectively. LY3023414 mainly inhibited osteoclast formation instead of mature osteoclast function. Moreover, it suppressed osteogenesis both in the early stage of differentiation and late stage of calcification. Similarly, gene knockdown of Akt isoforms by siRNA downregulated osteogenic and osteoclastogenic processes, indicating that Akt1 and Akt2 acted synergistically.
conclusionLY3023414 can suppress osteogenesis and osteoclastogenesis through inhibition of the PI3K/Akt/GSK3 signalling pathway, which highlights the potential benefits and side effects of LY3023414 for future clinical applications. Cite this article:
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