ArticleInternational journal of molecular sciences2019
FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
13 citing papers in PubMed, 22 citations in OpenAlex.
- Mechanosensitive Ion Channel PIEZO1 Suppresses BMP2-Induced Ossification of the Annulus Fibrosus Cells.JOR spine · 2026Article
- 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
- Spatiotemporal application of small molecules in fracture healing.Biomaterials translational · 2025Review
- Piezo1 protects against inflammatory bone loss via a unique CaFrontiers in immunology · 2025Article
- Bioactive materials forBioactive materials · 2024Review
- FKBP12 is a major regulator of ALK2 activity in multiple myeloma cells.Cell communication and signaling : CCS · 2023Article
- Integrated Proteotranscriptomics of the Hypothalamus Reveals Altered Regulation Associated with theBiology · 2022Article
- Article
- Repurposing existing products to accelerate injury recovery (REPAIR) of military relevant musculoskeletal conditions.Frontiers in bioengineering and biotechnology · 2022Article
- Article
- Bone-Forming Peptide-4 Induces Osteogenic Differentiation and VEGF Expression on Multipotent Bone Marrow Stromal Cells.Frontiers in bioengineering and biotechnology · 2021Article
- Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur.European cells & materials · 2020Article
- Correction: Sangadala, S. et al. FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis.International journal of molecular sciences · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Osteoinductive bone morphogenetic proteins (BMPs), including BMP-2, have a unique capability of mediating bone formation both in orthotopic and ectopic locations. Immunosuppresive macrolides have been shown to potentiate BMP-2 activity through FKBP12, but these have yet to translate to effective osteoinductive therapies. Herein, we show the osteogenic activity of FK506 as a stand-alone agent in direct comparison to BMP-2 both in vitro and in vivo. FK506 was capable of producing stand-alone alkaline phosphatase induction in C2C12 cells comparable to that seen with rhBMP-2. FK506 treatment activated the BMP receptor, as shown by increased pSmad1/5 levels, and produced significantly higher mRNA levels of the early response genes in BMP and TGF-β pathways. Additionally, the FK506 induction of alkaline phosphatase was shown to be resistant to Noggin treatment. In vivo osteogenic activity of FK506 was tested by local delivery on a collagen sponge in an ectopic subcutaneous implantation model in the rat. Dose responses of FK506 showed increasing levels of ectopic mineralization comparable to the mineral volume produced by BMP-2 delivery. These findings suggest that the use of FK506 can enhance osteoblastic differentiation in vitro and can induce mineralization when delivered locally in vivo.
Indexed as
Identifiers
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.