ArticleBone2012
TGF-β regulates sclerostin expression via the ECR5 enhancer.
Article in Bone, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 57 citations in OpenAlex.
- Discontinuing Long-Term Denosumab in Treating Fragile Bone: Why, for Whom, and How?Clinical pharmacology and therapeutics · 2026Review
- Spatially resolved osteoblast-traced transcriptomics uncovers TGF-β as a combination target with sclerostin in osteoporosis.Bone research · 2026Article
- Markers of Mineral Metabolism in Children With CKD Stages 2 to 5D.Kidney international reports · 2026Article
- Expression changes in Fasl-deficient calvaria-derived osteoblasts: an RNA-seq analysis.Scientific data · 2025Article
- The Multifaceted Effects of Osteocytic TGFβ Signaling on the Skeletal and Extraskeletal Functions of Bone.Current osteoporosis reports · 2023Review
- Paracrine and endocrine functions of osteocytes.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2023Review
- Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone-Vascular paradox, a therapeutic target, and a biomarker.Frontiers in physiology · 2023Review
- The Role of Sclerostin in Bone Diseases.Journal of clinical medicine · 2022Review
- Role of TGF-β1 in Fluoride-Treated Osteoblasts at Different Stages.Biological trace element research · 2022Article
- Association ofGenes · 2021Article
- Kindlin-2 mediates mechanotransduction in bone by regulating expression of Sclerostin in osteocytes.Communications biology · 2021Article
- Mechanosensitive Control of Articular Cartilage and Subchondral Bone Homeostasis in Mice Requires Osteocytic Transforming Growth Factor β Signaling.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Osteoporosis Treatment with Anti-Sclerostin Antibodies-Mechanisms of Action and Clinical Application.Journal of clinical medicine · 2021Review
- Article
- Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.International journal of molecular medicine · 2020Article
- Connexin 43 Channels in Osteocytes Regulate Bone Responses to Mechanical Unloading.Frontiers in physiology · 2020Article
- The Influence of Pro-Inflammatory Factors on Sclerostin and Dickkopf-1 Production in Human Dental Pulp Cells Under Hypoxic Conditions.Frontiers in bioengineering and biotechnology · 2019Article
- Systemic Activation of Activin A Signaling Causes Chronic Kidney Disease-Mineral Bone Disorder.International journal of molecular sciences · 2018Review
- TGF-Beta Signaling in Bone with Chronic Kidney Disease.International journal of molecular sciences · 2018Review
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Wnt signaling is critical for skeletal development and homeostasis. Sclerostin (Sost) has emerged as a potent inhibitor of Wnt signaling and, thereby, bone formation. Thus, strategies to reduce sclerostin expression may be used to treat osteoporosis or non-union fractures. Transforming growth factor-beta (TGF-β) elicits various effects upon the skeleton both in vitro and in vivo depending on the duration and timing of administration. In vitro and in vivo studies demonstrate that TGF-β increases osteoprogenitor differentiation but decreases matrix mineralization of committed osteoblasts. Because sclerostin decreases matrix mineralization, this study aimed to examine whether TGF-β achieves such inhibitory effects via transcriptional modulation of Sost. Using the UMR106.01 mature osteoblast cell line, we demonstrated that TGF-βTGF-β(1)-β(2)-β(3) and Activin A increase Sost transcript expression. Pharmacologic inhibition of Alk4/5/7 in vitro and in vivo decreased endogenous Sost expression, and siRNA against Alk4 and Alk5 demonstrated their requirement for endogenous Sost expression. TGF-β(1) targeted the Sost bone enhancer ECR5 and did not affect the transcriptional activity of the endogenous Sost promoter. These results indicate that TGF-β(1) controls Sost transcription in mature osteoblasts, suggesting that sclerostin may mediate the inhibitory effect of TGF-β upon osteoblast differentiation.
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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.