ArticlePloS one2013
Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Hand Osteoarthritis: Molecular Mechanisms, Randomized Controlled Trials, and the Future of Targeted Treatment.International journal of molecular sciences · 2025Review
- Vitamin A - discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility.Frontiers in endocrinology · 2024Review
- Understanding health disparities affecting people of West Central African descent in the United States: An evolutionary perspective.Evolutionary applications · 2023Review
- Gene Expression Profiles of Human Mesenchymal Stromal Cells Derived from Wharton's Jelly and Amniotic Membrane before and after Osteo-Induction Using NanoString Platform.Current issues in molecular biology · 2022Article
- Mechanisms of Feedback Regulation of Vitamin A Metabolism.Nutrients · 2022Review
- Capacitive interdigitated system of high osteoinductive/conductive performance for personalized acting-sensing implants.NPJ Regenerative medicine · 2021Article
- Signaling through retinoic acid receptors is essential for mammalian uterine receptivity and decidualization.JCI insight · 2021Article
- An overview of de novo bone generation in animal models.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Review
- Retinoids Repress Human Cardiovascular Cell Calcification With Evidence for Distinct Selective Retinoid Modulator Effects.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society.Frontiers in endocrinology · 2020Review
- Comparison between curcumin and all-trans retinoic acid in the osteogenic differentiation of mouse bone marrow mesenchymal stem cells.Experimental and therapeutic medicine · 2019Article
- Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopyBone reports · 2018Article
- Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018Review
- New insights and changing paradigms in the regulation of vitamin A metabolism in development.Wiley interdisciplinary reviews. Developmental biology · 2017Review
- Retinoid receptors in bone and their role in bone remodeling.Frontiers in endocrinology · 2015Review
- Retinaldehyde dehydrogenase 1 deficiency inhibits PPARγ-mediated bone loss and marrow adiposity.Bone · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.
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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.