ArticleThe Journal of biological chemistry2011
Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) protein regulates osteoblast differentiation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- The prevalence of ENPP1 deficiency in humans with Ossification of the Posterior Longitudinal Ligament and the preclinical efficacy of ENPP1 enzyme therapy in murine Ossification of the Posterior Longitudinal Ligament.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Microanatomy related biocidal activity at cellular resolution and bone reconstruction potential of PEG EGaIn nanocapsules.NPJ biofilms and microbiomes · 2025Article
- Calcified vs. Non-Calcified Tendinopathy of the Rotator Cuff: Clinical Presentations, Prognostic Implications, and Emerging Therapeutic Strategies.Journal of orthopaedics and sports medicine · 2025Article
- The ecto-nucleotide pyrophosphatase/phosphodiesterase 2 promotes early osteoblast differentiation and mineralization in stromal stem cells.American journal of physiology. Cell physiology · 2024Article
- ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.Annual review of pathology · 2024Review
- Cranial Neural Crest Specific Deletion ofInternational journal of molecular sciences · 2023Article
- Age-related decline in bone mineral transport and bone matrix proteins in osteoblasts from stromal stem cells.American journal of physiology. Cell physiology · 2023Article
- Human antibodies targeting ENPP1 as candidate therapeutics for cancers.Frontiers in immunology · 2023Article
- β-TCP from 3D-printed composite scaffolds acts as an effective phosphate source during osteogenic differentiation of human mesenchymal stromal cells.Frontiers in cell and developmental biology · 2023Article
- ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database.Human mutation · 2022Review
- Catalysis-Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Titanium Nanosurface with a Biomimetic Physical Microenvironment to Induce Endogenous Regeneration of the Periodontium.ACS applied materials & interfaces · 2022Article
- Identification of distinct non-myogenic skeletal-muscle-resident mesenchymal cell populations.Cell reports · 2022Article
- Deletion of the Pyrophosphate Generating Enzyme ENPP1 Rescues Craniofacial Abnormalities in the TNAPFrontiers in dental medicine · 2022Article
- Article
- Arterial Stiffness: A Focus on Vascular Calcification and Its Link to Bone Mineralization.Arteriosclerosis, thrombosis, and vascular biology · 2020Review
- Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy.The Clinical biochemist. Reviews · 2020Review
- Expression of Calcification and Extracellular Matrix Genes in the Cardiovascular System of the Healthy Domestic Sheep (Frontiers in genetics · 2020Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase-1) is an established regulator of tissue mineralization. Previous studies demonstrated that ENPP1 is expressed in differentiated osteoblasts and that ENPP1 influences matrix mineralization by increasing extracellular levels of inorganic pyrophosphate. ENPP1 is also expressed in osteoblastic precursor cells when stimulated with FGF2, but the role of ENPP1 in preosteoblastic and other precursor cells is unknown. Here we investigate the function of ENPP1 in preosteoblasts. We find that ENPP1 expression is critical for osteoblastic differentiation and that this effect is not mediated by changes in extracellular concentration levels of phosphate or pyrophosphate or ENPP1 catalytic activity. MC3T3E1(C4) preosteoblastic cells, in which ENPP1 expression was suppressed by ENPP1-specific shRNA, and calvarial cells isolated from Enpp1 knock-out mice show defective osteoblastic differentiation upon stimulation with ascorbate, as indicated by a lack of cellular morphological change, a lack of osteoblast marker gene expression, and an inability to mineralize matrix. Additionally, MC3T3E1(C4) cells, in which wild type or catalytic inactive ENPP1 expression was increased, exhibited an increased tendency to differentiate, as evidenced by increased osteoblast marker gene expression and increased mineralization. Notably, treatment of cells with inorganic phosphate or pyrophosphate inhibited, as opposed to enhanced, expression of multiple genes that are expressed in association with osteoblast differentiation, matrix deposition, and mineralization. Our results indicate that ENPP1 plays multiple and distinct roles in the development of mineralized tissues and that the influence of ENPP1 on osteoblast differentiation and gene expression may include a mechanism that is independent of its catalytic activity.
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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.