ArticleMolecular and cellular biology2009
The small molecule phenamil induces osteoblast differentiation and mineralization.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
40 citing papers in PubMed, 85 citations in OpenAlex.
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- Thermally-Induced Self-Agglomeration: Method and First Approaches to the Structural, Mechanical and Biological Characterization of Nanofiber Scaffolds.Current topics in medicinal chemistry · 2025Review
- The advancement of nanosystems for drug delivery in the prevention and treatment of dental caries.Frontiers in cellular and infection microbiology · 2025Review
- Anti-aging Metabolite-Based Polymeric Microparticles for Intracellular Drug Delivery and Bone Regeneration.Small science · 2024Article
- IL-1β contributes to the secretion of sclerostin by osteocytes and targeting sclerostin promotes spinal fusion at early stages.Journal of orthopaedic surgery and research · 2023Article
- Achievements in Mesoporous Bioactive Glasses for Biomedical Applications.Pharmaceutics · 2022Review
- Microgel-Assisted Delivery of Adenosine to Accelerate Fracture Healing.ACS biomaterials science & engineering · 2022Article
- Osteogenic Differentiation Effect of BMP-9 with Phenamil and Simvastatin on Intact Human Amniotic Epithelial Stem CellsIranian biomedical journal · 2022Article
- Cell-Based Double-Screening Method to Identify a Reliable Candidate for Osteogenesis-Targeting Compounds.Biomedicines · 2022Article
- Exosomal miRNAs from Prostate Cancer Impair Osteoblast Function in Mice.International journal of molecular sciences · 2022Article
- The Twofold Role of Osteogenic Small Molecules in Parkinson's Disease Therapeutics: Crosstalk of Osteogenesis and Neurogenesis.BioMed research international · 2022Review
- An Elastic Mineralized 3D Electrospun PCL Nanofibrous Scaffold for Drug Release and Bone Tissue Engineering.ACS applied bio materials · 2021Article
- Engineering the MSC Secretome: A Hydrogel Focused Approach.Advanced healthcare materials · 2021Review
- Role of Curcuminoids and Tricalcium Phosphate Ceramic in Rat Spinal Fusion.Tissue engineering. Part C, Methods · 2020Article
- Smurf1 Silencing Using a LNA-ASOs/Lipid Nanoparticle System to Promote Bone Regeneration.Stem cells translational medicine · 2019Article
- Current advances for bone regeneration based on tissue engineering strategies.Frontiers of medicine · 2019Review
- Enhanced Cellular Uptake Of Phenamil Through Inclusion Complex With Histidine Functionalized β-Cyclodextrin As Penetrative Osteoinductive Agent.International journal of nanomedicine · 2019Article
- Aucubin suppresses Titanium particles‑mediated apoptosis of MC3T3‑E1 cells and facilitates osteogenesis by affecting the BMP2/Smads/RunX2 signaling pathway.Molecular medicine reports · 2018Article
- Progress of Regenerative Therapy in Orthopedics.Current osteoporosis reports · 2018Review
- Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2-Induced Bone Formation.Applied materials today · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Stimulation of osteoblast differentiation from mesenchymal stem cells is a potential strategy for bone repair. Bone morphogenetic proteins (BMPs) that induce osteoblastic differentiation have been successfully used in humans to treat fractures. Here we outline a new approach to the stimulation of osteoblast differentiation using small molecules that stimulate BMP activity. We have identified the amiloride derivative phenamil as a stimulator of osteoblast differentiation and mineralization. Remarkably, phenamil acts cooperatively with BMPs to induce the expression of BMP target genes, osteogenic markers, and matrix mineralization in both mesenchymal stem cell lines and calvarial organ cultures. Transcriptional profiling of cells treated with phenamil led to the identification of tribbles homolog 3 (Trb3) as a mediator of its effects. Trb3 is induced by phenamil selectively in cells with osteoblastic potential. Both Trb3 and phenamil stabilize the expression of SMAD, the critical transcription factor in BMP signaling, by promoting the degradation of SMAD ubiquitin regulatory factor 1. Small interfering RNA-mediated knockdown of Trb3 blunts the effects of phenamil on BMP signaling and osteogenesis. Thus, phenamil induces osteogenic differentiation, at least in part, through Trb3-dependent promotion of BMP action. The synergistic use of small molecules such as phenamil along with BMPs may provide new strategies for the promotion of bone healing.
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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.