ArticleJournal of cellular and molecular medicine2015
BMP-9 regulates the osteoblastic differentiation and calcification of vascular smooth muscle cells through an ALK1 mediated pathway.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 65 citations in OpenAlex.
- Article
- Endothelial BMP6 Drives Hemodynamic-Dependent VSMCs Calcification in Carotid Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Distribution, extent, and calculated age of initiation of coronary artery calcification.Polish journal of radiology · 2026Article
- The Association of Circulating Bone Morphogenetic Protein 9 and Arterial Stiffness in Hypertensive Patients.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- Enhanced Osteoinduction and Osteogenesis Promotion by Bovine Freeze-Dried Bone Combined withACS omega · 2025Article
- Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.Nature reviews. Nephrology · 2024Review
- Vascular Calcification Heterogeneity from Bench to Bedside: Implications for Manifestations, Pathogenesis, and Treatment Considerations.Aging and disease · 2024Review
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Addition of heparin binding sites strongly increases the bone forming capabilities of BMP9Bioactive materials · 2023Article
- Kielin/chordin-like protein deficiency causes cardiac aging in male mice.Journal of molecular medicine (Berlin, Germany) · 2023Article
- p53 Regulates Mitochondrial Dynamics in Vascular Smooth Muscle Cell Calcification.International journal of molecular sciences · 2023Article
- Insights into bone morphogenetic proteins in cardiovascular diseases.Frontiers in pharmacology · 2023Review
- Cdon suppresses vascular smooth muscle calcification via repression of the Wnt/Runx2 Axis.Experimental & molecular medicine · 2023Article
- 3-Arylcoumarin inhibits vascular calcification by inhibiting the generation of AGEs and anti-oxidative stress.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- The potential regulatory role of BMP9 in inflammatory responses.Genes & diseases · 2022Review
- The proliferation and migration of atherosclerosis-related HVSMCs were inhibited by downregulation of lncRNA XIST via regulation of the miR-761/BMP9 axis.The Kaohsiung journal of medical sciences · 2022Article
- Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway.International journal of molecular sciences · 2021Article
- Secondary Hyperparathyroidism in Chronic Kidney Disease: Pathophysiology and Management.Cureus · 2021Review
- Regulatory role of mammalian target of rapamycin signaling in exosome secretion and osteogenic changes in smooth muscle cells lacking acid ceramidase gene.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice.Journal of cellular physiology · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The process of vascular calcification shares many similarities with that of physiological skeletal mineralization, and involves the deposition of hydroxyapatite crystals in arteries. However, the cellular mechanisms responsible have yet to be fully explained. Bone morphogenetic protein (BMP-9) has been shown to exert direct effects on both bone development and vascular function. In the present study, we have investigated the role of BMP-9 in vascular smooth muscle cell (VSMC) calcification. Vessel calcification in chronic kidney disease (CKD) begins pre-dialysis, with factors specific to the dialysis milieu triggering accelerated calcification. Intriguingly, BMP-9 was markedly elevated in serum from CKD children on dialysis. Furthermore, in vitro studies revealed that BMP-9 treatment causes a significant increase in VSMC calcium content, alkaline phosphatase (ALP) activity and mRNA expression of osteogenic markers. BMP-9-induced calcium deposition was significantly reduced following treatment with the ALP inhibitor 2,5-Dimethoxy-N-(quinolin-3-yl) benzenesulfonamide confirming the mediatory role of ALP in this process. The inhibition of ALK1 signalling using a soluble chimeric protein significantly reduced calcium deposition and ALP activity, confirming that BMP-9 is a physiological ALK1 ligand. Signal transduction studies revealed that BMP-9 induced Smad2, Smad3 and Smad1/5/8 phosphorylation. As these Smad proteins directly bind to Smad4 to activate target genes, siRNA studies were subsequently undertaken to examine the functional role of Smad4 in VSMC calcification. Smad4-siRNA transfection induced a significant reduction in ALP activity and calcium deposition. These novel data demonstrate that BMP-9 induces VSMC osteogenic differentiation and calcification via ALK1, Smad and ALP dependent mechanisms. This may identify new potential therapeutic strategies for clinical intervention.
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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.