ArticleBone2012
A novel library screen identifies immunosuppressors that promote osteoblast differentiation.
Article in Bone, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Osteogenic Small Molecule FK506 for Enhanced Bone Formation in a Rabbit Ankle Fusion Model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- TGF-β3 Restrains Osteoclastic Resorption Through Autophagy.Bioengineering (Basel, Switzerland) · 2024Article
- Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis: Implications for bone health.World journal of stem cells · 2024Article
- Small-Molecule Probes as Pharmacological Tools for the Bone Morphogenetic Protein Signaling Pathway.ACS pharmacology & translational science · 2023Review
- Genetic Evidence Supporting a Causal Association Between mTOR-Dependent EIF-4E Circulating Protein Level and Osteoporosis.Advances in therapy · 2023Article
- Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- 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
- Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.BioFactors (Oxford, England) · 2023Article
- Effects of Scoparone on differentiation, adhesion, migration, autophagy and mineralization through the osteogenic signalling pathways.Journal of cellular and molecular medicine · 2022Article
- Effects of Triterpene Soyasapogenol B fromInternational journal of molecular sciences · 2022Article
- Cell-Based Double-Screening Method to Identify a Reliable Candidate for Osteogenesis-Targeting Compounds.Biomedicines · 2022Article
- Regulation of osteoblast autophagy based on PI3K/AKT/mTOR signaling pathway study on the effect of β-ecdysterone on fracture healing.Journal of orthopaedic surgery and research · 2021Article
- Rapamycin could increase the effects of melatonin against age-dependent bone loss.Zeitschrift fur Gerontologie und Geriatrie · 2020Article
- Role of Curcuminoids and Tricalcium Phosphate Ceramic in Rat Spinal Fusion.Tissue engineering. Part C, Methods · 2020Article
- Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur.European cells & materials · 2020Article
- Autophagy in fate determination of mesenchymal stem cells and bone remodeling.World journal of stem cells · 2020Review
- Puerarin promotes the viability and differentiation of MC3T3-E1 cells by enhancing LC3B-mediated autophagy through downregulation of miR-204.Experimental and therapeutic medicine · 2020Article
- [Role of autophagy in the pathogenesis of periodontitis].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2019Review
- Discovery of a Small Molecule Promoting Mouse and Human Osteoblast Differentiation via Activation of p38 MAPK-β.Cell chemical biology · 2019Article
- FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Bone homeostasis can be compromised by an increase in osteoclast-mediated resorption and/or a decrease in osteoblast-mediated bone deposition. While many efforts have focused on treating osteoclast resorption, there has been less emphasis on identifying strategies for promoting osteoblast function. Herein, we describe a high-throughput screening assay to select for small molecules that augment bone morphogenetic protein-2 (BMP-2)-mediated osteoblast lineage commitment. After an initial screen of 5405 compounds; consisting of FDA-approved drugs, known bioactives, and compounds with novel chemical makeup, we identified 45 small molecules that promoted osteoblast commitment. Of the 45 candidates, there was a broad array of classes that included nine retinoid analogs/derivatives and four immunosuppressants, notably rapamycin and FK-506, which were chosen for further study. Treatment of osteoblast precursor cells with rapamycin or FK-506, either alone, or synergistically with BMP-2, increased levels of phospho-Smad 1/5/8 protein and transcription of Runx-2, Osx and Smad-7, consistent with a role in promoting osteoblast differentiation. Only FK-506 was able to enhance osteocalcin transcripts and Alizarin Red staining, both late markers for differentiation. When osteoblast differentiation was suppressed with exogenous TGF-β1 treatment, rapamycin (but not FK-506) was able to rescue expression of differentiation markers, indicating distinct but overlapping activity of these compounds. Collectively, these data add to an understanding of pathways engaged in osteoblastogenesis, support a role for non-redundant immunosuppressant signaling, and provide a novel approach for the discovery of potentially therapeutic compounds that affect bone remodeling.
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What OpenQuestion holds
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.