ArticleJournal of orthopaedic surgery and research2021
Homoharringtonine inhibits fibroblasts proliferation, extracellular matrix production and reduces surgery-induced knee arthrofibrosis via PI3K/AKT/mTOR pathway-mediated apoptosis.
Article in Journal of orthopaedic surgery and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Transcriptome-Guided Drug Repurposing Identifies Homoharringtonine (HHT) as a Candidate for Radiation-Induced Pulmonary Fibrosis.Pharmaceutics · 2025Article
- Homoharringtonine exerts anti-silicosis potential by inhibiting the CCR1 and PI3K/AKT signaling pathways in lung fibroblasts.Journal of biomedical research · 2025Article
- CCN2 mediates fibroblast-macrophage interaction in knee arthrofibrosis based on single-cell RNA-seq analysis.Bone research · 2025Article
- Homoharringtonine: mechanisms, clinical applications and research progress.Frontiers in oncology · 2025Review
- A prognostic model of lung adenocarcinoma constructed based on circadian rhythm genes and its potential clinical significance.Frontiers in oncology · 2025Article
- Computational screening of biomarkers and potential drugs for arthrofibrosis based on combination of sequencing and large nature language model.Journal of orthopaedic translation · 2024Article
- Prediction and Demonstration of Retinoic Acid Receptor Agonist Ch55 as an Antifibrotic Agent in the Dermis.The Journal of investigative dermatology · 2023Article
- Convergent Genomic Signatures of Cashmere Traits: Evidence for Natural and Artificial Selection.International journal of molecular sciences · 2023Article
- Biochemical markers of postsurgical knee arthrofibrosis: A systematic review.Journal of orthopaedics · 2023Review
- Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFβ1 stimulation.Journal of cellular biochemistry · 2022Article
- The Fibrotic Effects of TMAO on Human Renal Fibroblasts Is Mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR Pathway.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe prevention of surgery-induced intraarticular fibrosis remains a challenge following orthopedic surgery. Homoharringtonine (HHT) has been reported to have positive effects in preventing various kinds of fibrosis. However, little is known regarding its effect as well as the potential mechanism of HHT in preventing surgery-induced intraarticular fibrosis.
methodsVarious concentrations of HHTs were locally applied in vivo to reduce knee intraarticular fibrosis in rabbits. Histological macroscopic assessments such as hematoxylin and eosin (HE) staining, Masson's trichrome staining, and Picric-sirius red polarized light were used to evaluate the effect of HHT in reducing intraarticular fibrosis. CCK-8, cell cycle assay, and EdU incorporation assay were used in vitro to detect HHT's effect on inhibiting fibroblast viability and proliferation. The effect of HHT on fibroblast differentiation, extracellular matrix production, and apoptosis were evaluated by western blot, flow cytometry, immunofluorescent staining, and TUNEL analysis. Moreover, the expressions of PI3K/AKT/mTOR signaling pathway were detected.
resultsThe results demonstrated that HHT could reduce the formation of intraarticular fibrosis. HHT was also found to induce fibroblast apoptotic cell death in a dose- and time-dependent manner in vitro. Moreover, HHT could effectively inhibit the production of the extracellular matrix secreted by fibroblasts and inhibited the expression of p-PI3K, p-AKT, and p-mTOR in a dose-dependent manner. After treating with insulin-like growth factor-1 (IGF-1), an activator of the PI3K/AKT axis, the expressions of pro-apoptosis-related proteins were decreased, and the fibroblast apoptosis rate was also inhibited.
conclusionsIn conclusion, this study demonstrated that HHT could reduce the formation of intraarticular fibrosis through the inhibition of fibroblast proliferation, extracellular matrix production, and the induction of fibroblast apoptotic cell death. Furthermore, its potential mechanism may be through the suppression of the PI3K/AKT/mTOR signaling pathway.
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