ArticleNature medicine2011
Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 4 registered trials, which are not on this map. Cited by 205 papers, 1 of them a synthesis that pooled it.
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.
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of a RARγ-Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
A Phase 2, Open-Label Extension, Efficacy and Safety Study of a Retinoic Acid Receptor Gamma (RARγ) Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
A Phase 2, In-Home, Safety and Efficacy Evaluation of Episodic Administration of Open-Label Palovarotene in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
Who cites it
205 citing papers in PubMed, 1 synthesis or guideline pooled it, 333 citations in OpenAlex.
- Incidence of heterotopic ossification following total hip arthroplasty by approach: a systematic review.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2024Pooled it
- A Pharmacokinetic, Safety, and Tolerability Trial of Palovarotene in Healthy Japanese and Non-Japanese Participants.European journal of drug metabolism and pharmacokinetics · 2023Trial
- Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP): Results of a Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Trial
- Pathogenic transcriptional reprogramming of fibro-adipogenic progenitors in mice with FOP and its mitigation by inhibition of ACVR1 and activin A.bioRxiv : the preprint server for biology · 2026Article
- Retinoic Acid Receptor γ Is a Ligand-Activated Gatekeeper to Stem Cell Developmental Progression.International journal of molecular sciences · 2026Review
- Orthopedic preoperative evaluation and surgical strategies of hereditary multiple osteochondromas involving the spinal region.EFORT open reviews · 2026Review
- Evaluation of Mass Spectrometry Compatible Reagents for Determining Small Molecule Loading in Poly(lactic acid) Nanoparticles.Pharmaceutical research · 2026Article
- Retinoic Acid Receptor γ Activity Plays a Critical Role in Regulating Early Mouse Gastruloid Development.International journal of molecular sciences · 2026Article
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.Bone research · 2026Article
- The role of RARG in solid tumor progression and therapeutic potential.Discover oncology · 2026Review
- The Influences of RARγ on the Behavior of Normal and Cancer Stem Cells.International journal of molecular sciences · 2026Review
- The relationship between OPLL and metabolic disorders.Bone research · 2025Review
- Article
- Vitamin A Deficiency Induces Congenital Vertebral Malformation via Retinoic Acid Signaling Mediated Sclerotome Dysplasia.Neurospine · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Article
- The Emerging Oncogenic Role of RARγ: From Stem Cell Regulation to a Potential Cancer Therapy.International journal of molecular sciences · 2025Review
- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- Retinoid-impregnated nanoparticles enable control of bone growth by site-specific modulation of endochondral ossification in mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
145 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Heterotopic ossification consists of ectopic bone formation within soft tissues after surgery or trauma. It can have debilitating consequences, but there is no definitive cure. Here we show that heterotopic ossification was essentially prevented in mice receiving a nuclear retinoic acid receptor-γ (RAR-γ) agonist. Side effects were minimal, and there was no significant rebound effect. To uncover the mechanisms of these responses, we treated mouse mesenchymal stem cells with an RAR-γ agonist and transplanted them into nude mice. Whereas control cells formed ectopic bone masses, cells that had been pretreated with the RAR-γ agonist did not, suggesting that they had lost their skeletogenic potential. The cells became unresponsive to rBMP-2 treatment in vitro and showed decreases in phosphorylation of Smad1, Smad5 and Smad8 and in overall levels of Smad proteins. In addition, an RAR-γ agonist blocked heterotopic ossification in transgenic mice expressing activin receptor-like kinase-2 (ALK2) Q207D, a constitutively active form of the receptor that is related to ALK2 R206H found in individuals with fibrodysplasia ossificans progressiva. The data indicate that RAR-γ agonists are potent inhibitors of heterotopic ossification in mouse models and, thus, may also be effective against injury-induced and congenital heterotopic ossification in humans.
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.