ArticleBone2010
Inorganic pyrophosphatase induces type I collagen in osteoblasts.
Article in Bone, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- PPa1 insufficiency drives lysosomal storage disease and inflammatory macrophage expansion in the bone marrow.bioRxiv : the preprint server for biology · 2026Article
- Pyrophosphate Regulates Multilineage Differentiation in Stem Cells From Human Exfoliated Deciduous Teeth.Clinical and experimental dental research · 2025Article
- Macrophage-Derived Type 1 IFN, Renal Tubular Epithelial Cell Polyploidization, and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2025Article
- Methionine supplementation-induced alteration of sheep seminal plasma miRNAs and proteome.Journal of animal science · 2025Article
- PPA1 promotes adipogenesis by regulating the stability of C/EBPs.Cell death and differentiation · 2024Article
- PPA1, an energy metabolism initiator, plays an important role in the progression of malignant tumors.Frontiers in oncology · 2022Review
- Cystatin-like protein of sweet orange (CsinCPI-2) modulates pre-osteoblast differentiation via β-Catenin involvement.Journal of materials science. Materials in medicine · 2021Article
- Aggregation-Induced Emission of Au/Ag Alloy Nanoclusters for Fluorescence Detection of Inorganic Pyrophosphate and Pyrophosphatase Activity.Frontiers in bioengineering and biotechnology · 2020Article
- PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner.Oncogenesis · 2019Article
- Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Rare Co-occurrence of Beta-Thalassemia andFrontiers in medicine · 2019Article
- ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the generation of AMP.Experimental & molecular medicine · 2018Article
- Clinical significance and functional validation of inorganic pyrophosphatase in diffuse large B cell lymphoma in humans.Cytotechnology · 2018Article
- Silencing PPA1 inhibits human epithelial ovarian cancer metastasis by suppressing the Wnt/β-catenin signaling pathway.Oncotarget · 2017Article
- Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro.Tissue engineering. Part B, Reviews · 2017Article
- Finding the culprit: who is turning hearts to stone?Stem cell investigation · 2017Article
- Clinical significance and functional validation of PPA1 in various tumors.Cancer medicine · 2016Article
- Skeletal Mineralization Deficits and Impaired Biogenesis and Function of Chondrocyte-Derived Matrix Vesicles in Phospho1(-/-) and Phospho1/Pi t1 Double-Knockout Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline Phosphatase Activity in Osteoblasts.PloS one · 2016Article
- Elastin governs the mechanical response of medial collateral ligament under shear and transverse tensile loading.Acta biomaterialia · 2015Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
introductionThe physiologic selectivity of calcification in bone tissue reflects selective co-expression by osteoblasts of fibrillar collagen I and of tissue nonspecific alkaline phosphatase (TNAP), which hydrolyzes the calcification inhibitor pyrophosphate (PP(i)) and generates phosphate (P(i)). Humans and mice deficient in the PP(i)-generating ecto-enzyme NPP1 demonstrate soft tissue calcification, occurring at sites of extracellular matrix expansion. Significantly, the function in osteoblasts of cytosolic inorganic pyrophosphatase (abbreviated iPP(i)ase), which generates P(i) via PP(i) hydrolysis with neutral pH optimum, remains unknown. We assessed iPP(i)ase in Enpp1(-/-) and wild type (WT) mouse osteoblasts and we tested the hypothesis that iPP(i)ase regulates collagen I expression.
methodsWe treated mouse calvarial osteoblasts with ascorbate and beta-glycerol phosphate to promote calcification, and we assessed cytosolic P(i) and PP(i) levels, sodium-dependent P(i) uptake, Pit-1 P(i) co-transporter expression, and iPP(i)ase and TNAP activity and expression. We also assessed the function of transfected Ppa1 in osteoblasts.
resultsInorganic pyrophosphatase but not TNAP was elevated in Enpp1(-/-) calvariae in situ. Cultured primary Enpp1(-/-) calvarial osteoblasts demonstrated increased calcification despite flat TNAP activity rather than physiologic TNAP up-regulation seen in WT osteoblasts. Despite decreased cytosolic PP(i) in early culture, Enpp1(-/-) osteoblasts maintained cytosolic P(i) levels comparable to WT osteoblasts, in association with increased iPP(i)ase, enhanced sodium-dependent P(i) uptake and expression of Pit-1, and markedly increased collagen I synthesis. Suppression of collagen synthesis in Enpp1(-/-) osteoblasts using 3,4-dehydroproline markedly suppressed calcification. Last, transfection of Ppa1 in WT osteoblasts increased cytosolic P(i) and decreased cytosolic but not extracellular PP(i), and induced both collagen I synthesis and calcification.
conclusionsIncreased iPP(i)ase is associated with "P(i) hunger" and increased calcification by NPP1-deficient osteoblasts. Furthermore, iPP(i)ase induces collagen I at the levels of mRNA expression and synthesis and, unlike TNAP, stimulates calcification by osteoblasts without reducing the extracellular concentration of the hydroxyapatite crystal inhibitor PP(i).
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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.