ArticleExperimental & molecular medicine2016
Smad4 controls bone homeostasis through regulation of osteoblast/osteocyte viability.
Article in Experimental & molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Comparison In Vitro Study on the Interface between Skin and Bone Cell Cultures and Microporous Titanium Samples Manufactured with 3D Printing Technology Versus Sintered Samples.Nanomaterials (Basel, Switzerland) · 2024Article
- Unraveling the Link of Altered TGFβ Signaling with Scoliotic Vertebral Malformations in Osteogenesis Imperfecta: A Comprehensive Review.Journal of clinical medicine · 2024Review
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Fluid shear stress-induced down-regulation of miR-146a-5p inhibits osteoblast apoptosis via targeting SMAD4.Physiological research · 2022Article
- 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
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- Quantitative proteomics reveals the effect of Yigu decoction (YGD) on protein expression in bone tissue.Clinical proteomics · 2021Article
- mRNA-miRNA-lncRNA Regulatory Network in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Article
- YAP/TAZ in Bone and Cartilage Biology.Frontiers in cell and developmental biology · 2021Review
- Polydopamine coating with static magnetic field promotes the osteogenic differentiation of human bone-derived mesenchymal stem cells on three-dimensional printed porous titanium scaffolds by upregulation of the BMP-Smads signaling pathway.American journal of translational research · 2020Article
- The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway.International journal of nanomedicine · 2020Article
- Glucagon-like peptide 2 decreases osteoclasts by stimulating apoptosis dependent on nitric oxide synthase.Cell proliferation · 2018Article
- Osterix regulates corticalization for longitudinal bone growth via integrin β3 expression.Experimental & molecular medicine · 2018Article
- Liraglutide exerts a bone-protective effect in ovariectomized rats with streptozotocin-induced diabetes by inhibiting osteoclastogenesis.Experimental and therapeutic medicine · 2018Article
- [Regulation of microRNA-17-92 cluster on bone development, remodeling, and metabolism].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2017Review
- Three-dimensional system enabling the maintenance and directed differentiation of pluripotent stem cells under defined conditions.Science advances · 2017Article
- Differential Impacts of Alternative Splicing Networks on Apoptosis.International journal of molecular sciences · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulation of osteoblast and osteocyte viability is essential for bone homeostasis. Smad4, a major transducer of bone morphogenetic protein and transforming growth factor-β signaling pathways, regulates apoptosis in various cell types through a mitochondrial pathway. However, it remains poorly understood whether Smad4 is necessary for the regulation of osteoblast and osteocyte viability. In this study, we analyzed Smad4Δ(Os) mice, in which Smad4 was subjected to tissue-specific disruption under the control of the 2.3-kb Col1a1 promoter, to understand the functional significance of Smad4 in regulating osteoblast/osteocyte viability during bone formation and remodeling. Smad4Δ(Os) mice showed a significant increase in osteoblast number and osteocyte density in the trabecular and cortical regions of the femur, whereas osteoclast activity was significantly decreased. The proliferation of osteoblasts/osteocytes did not alter, as shown by measuring 5'-bromo-2'deoxyuridine incorporation. By contrast, the percentage of TUNEL-positive cells decreased, together with a decrease in the Bax/Bcl-2 ratio and in the proteolytic cleavage of caspase 3, in Smad4Δ(Os) mice. Apoptosis in isolated calvaria cells from Smad4Δ(Os) mice decreased after differentiation, which was consistent with the results of the TUNEL assay and western blotting in Smad4Δ(Os) mice. Conversely, osteoblast cells overexpressing Smad4 showed increased apoptosis. In an apoptosis induction model of Smad4Δ(Os) mice, osteoblasts/osteocytes were more resistant to apoptosis than were control cells, and, consequently, bone remodeling was attenuated. These findings indicate that Smad4 has a significant role in regulating osteoblast/osteocyte viability and therefore controls bone homeostasis.
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