ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2013
Pharmacological inhibition of PHOSPHO1 suppresses vascular smooth muscle cell calcification.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.Human molecular genetics · 2016Pooled it
- Lansoprazole Increases Inorganic Pyrophosphate in Patients with Pseudoxanthoma Elasticum: A Double-Blind, Randomized, Placebo-Controlled Crossover Trial.International journal of molecular sciences · 2023Trial
- Lactylation: a metabolic-epigenetic driver in atherosclerosis pathogenesis and therapeutic targeting.Frontiers in cardiovascular medicine · 2026Review
- TNAP dephosphorylates phosphocholine and phosphoethanolamine and participates in triglyceride transport from the liver to the bloodstream.Communications biology · 2025Article
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- The emerging roles of PHOSPHO1 and its regulated phospholipid homeostasis in metabolic disorders.Frontiers in physiology · 2022Review
- Matrix Vesicles as a Therapeutic Target for Vascular Calcification.Frontiers in cell and developmental biology · 2022Review
- The Physiological and Pathological Role of Tissue Nonspecific Alkaline Phosphatase beyond Mineralization.Biomolecules · 2021Review
- Biomolecules Orchestrating Cardiovascular Calcification.Biomolecules · 2021Review
- Poor bone matrix quality: What can be done about it?Current osteoporosis reports · 2021Review
- From organic and inorganic phosphates to valvular and vascular calcifications.Cardiovascular research · 2021Review
- Article
- The Elusive Origin of Atherosclerotic Plaque Calcification.Frontiers in cell and developmental biology · 2021Review
- Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways.International journal of molecular sciences · 2020Review
- Article
- How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond.JBMR plus · 2019Review
- Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target.Current cardiology reviews · 2019Review
- Matrix vesicles from chondrocytes and osteoblasts: Their biogenesis, properties, functions and biomimetic models.Biochimica et biophysica acta. General subjects · 2018Review
- Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications.Frontiers in endocrinology · 2018Review
- Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification.Journal of visualized experiments : JoVE · 2017Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Medial vascular calcification (MVC) is common in patients with chronic kidney disease, obesity, and aging. MVC is an actively regulated process that resembles skeletal mineralization, resulting from chondro-osteogenic transformation of vascular smooth muscle cells (VSMCs). Here, we used mineralizing murine VSMCs to study the expression of PHOSPHO1, a phosphatase that participates in the first step of matrix vesicles-mediated initiation of mineralization during endochondral ossification. Wild-type (WT) VSMCs cultured under calcifying conditions exhibited increased Phospho1 gene expression and Phospho1(-/-) VSMCs failed to mineralize in vitro. Using natural PHOSPHO1 substrates, potent and specific inhibitors of PHOSPHO1 were identified via high-throughput screening and mechanistic analysis and two of these inhibitors, designated MLS-0390838 and MLS-0263839, were selected for further analysis. Their effectiveness in preventing VSMC calcification by targeting PHOSPHO1 function was assessed, alone and in combination with a potent tissue-nonspecific alkaline phosphatase (TNAP) inhibitor MLS-0038949. PHOSPHO1 inhibition by MLS-0263839 in mineralizing WT cells (cultured with added inorganic phosphate) reduced calcification in culture to 41.8% ± 2.0% of control. Combined inhibition of PHOSPHO1 by MLS-0263839 and TNAP by MLS-0038949 significantly reduced calcification to 20.9% ± 0.74% of control. Furthermore, the dual inhibition strategy affected the expression of several mineralization-related enzymes while increasing expression of the smooth muscle cell marker Acta2. We conclude that PHOSPHO1 plays a critical role in VSMC mineralization and that "phosphatase inhibition" may be a useful therapeutic strategy to reduce MVC.
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