ArticleScientific reports2016
Smad4 is required to inhibit osteoclastogenesis and maintain bone mass.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 21 citations in OpenAlex.
- Amuc_1473 Links Gut Microbes to Skeletal Homeostasis and Counteracts Multifactorial Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DC-STAMP and OC-STAMP cooperatively regulate osteoclast and foreign body giant cell cell-cell fusion.Journal of bone and mineral metabolism · 2026Article
- The Role of Oral and Gut Microbiota in Bone Health: Insights from Bacterial Extracellular Vesicles.Microorganisms · 2025Review
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Pulsed Electromagnetic Field Promotes Bone Anabolism in Postmenopausal Osteoporosis through the miR-6976/BMP/Smad4 Axis.Journal of tissue engineering and regenerative medicine · 2023Article
- TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis.Nature communications · 2022Article
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- The Role Of BMPs in the Regulation of Osteoclasts Resorption and Bone Remodeling: From Experimental Models to Clinical Applications.Frontiers in immunology · 2022Review
- The Bone Morphogenetic Protein Pathway: The Osteoclastic Perspective.Frontiers in cell and developmental biology · 2020Review
- Bone morphogenetic proteins: Their role in regulating osteoclast differentiation.Bone reports · 2019Review
- Transcriptomic Data Identified Key Transcription Factors for Osteoporosis in Caucasian Women.Calcified tissue international · 2018Article
- The nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls. TGFβ1-activation induced expression of Irf8 and Bcl6, both of which encode factors inhibiting osteoclastogenesis, by blocking their negative regulator, Prdm1, in osteoclasts in a Smad4-dependent manner. Reduced bone-mass and accelerated osteoclastogenesis seen in Smad4-cKO were abrogated by Prdm1 deletion. Administration of latent-TGFβ1-Fc to wild-type mice antagonized LPS-induced bone destruction in a model of activated osteoclast-mediated bone destruction. Thus, latent-TGFβ1-Fc could serve as a promising new therapeutic agent in bone diseases marked by excessive resorption.
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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.