ArticleBone2014
Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice.
Article in Bone, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Six cases ofJBMR plus · 2025Article
- Improvements in hearing loss with bone-targeted enzyme replacement therapy are associated with corrected hypomineralization and osteocyte properties of auditory ossicles in Enpp1-deficient mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Decoding dental mesenchymal stem cells diversity: single-cell transcriptomics maps heterogeneity in molar development.Frontiers in cell and developmental biology · 2025Review
- Enpp1 mutations promote upregulation of hedgehog signaling in heterotopic ossification with aging.Journal of bone and mineral metabolism · 2024Article
- The ecto-nucleotide pyrophosphatase/phosphodiesterase 2 promotes early osteoblast differentiation and mineralization in stromal stem cells.American journal of physiology. Cell physiology · 2024Article
- The Purinergic Nature of Pseudoxanthoma Elasticum.Biology · 2024Review
- ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.Annual review of pathology · 2024Review
- Heparins are potent inhibitors of ectonucleotide pyrophosphatase/phospho-diesterase-1 (NPP1) - a promising target for the immunotherapy of cancer.Frontiers in immunology · 2023Article
- Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces.Bone reports · 2022Review
- Disorders of phosphate homeostasis in children, part 1: primer on mineral ion homeostasis and the roles of phosphate in skeletal biology.Pediatric radiology · 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
- Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI).Orphanet journal of rare diseases · 2022Article
- Deconvolution of the hematopoietic stem cell microenvironment reveals a high degree of specialization and conservation.iScience · 2022Article
- Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review.Frontiers in genetics · 2022Review
- Generalized Arterial Calcification of Infancy (GACI): Optimizing Care with a Multidisciplinary Approach.Journal of multidisciplinary healthcare · 2022Review
- Enzymatic Approach in Calcium Phosphate Biomineralization: A Contribution to Reconcile the Physicochemical with the Physiological View.International journal of molecular sciences · 2021Review
- Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice.Journal of cellular physiology · 2021Article
- Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse nucleotide triphosphates to the corresponding nucleotide monophosphates and the mineralisation inhibitor, pyrophosphate (PPi). This study examined the role of NPP1 in osteocytes, osteoclasts and cortical bone, using a mouse model lacking NPP1 (Enpp1(-/-)). We used microcomputed tomography (μCT) to investigate how NPP1 deletion affects cortical bone structure; excised humerus bones from 8, 15 and 22-week old mice were scanned at 0.9 μm. Although no changes were evident in the cortical bone of 8-week old Enpp1(-/-) mice, significant differences were observed in older animals. Cortical bone volume was decreased 28% in 22-week Enpp1(-/-) mice, whilst cortical porosity was reduced 30% and 60% at 15 and 22-weeks, respectively. This was accompanied by up to a 15% decrease in closed pore diameter and a 55% reduction in the number of pores. Cortical thickness was reduced up to 35% in 15 and 22-week Enpp1(-/-) animals and the endosteal diameter was increased up to 23%. Thus, the cortical bone from Enpp1(-/-) mice was thinner and less porous, with a larger marrow space. Scanning electron microscopy (SEM) revealed a decrease in the size and number of blood vessel channels in the cortical bone as well as a 40% reduction in the mean plan area of osteocyte lacunae. We noted that the number of viable osteocytes isolated from the long bones of Enpp1(-/-) mice was decreased ≤50%. In contrast, osteoclast formation and resorptive activity were unaffected by NPP1 deletion. μCT and histological analysis of Enpp1(-/-) mice also revealed calcification of the joints and vertebrae as well as soft tissues including the whisker follicles, ear pinna and trachea. This calcification worsened as the animals aged. Together, these data highlight the key role of NPP1 in regulating calcification of both soft and skeletal tissues.
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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.