ArticlePLoS genetics2020
The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 83 citations in OpenAlex.
- Assessing the genetic potential of a milk mid-infrared prediction of heat stress response in dairy cows using a temperature-humidity index-independent approach.JDS communications · 2026Article
- Citrate Transporter NaCT and Enamel Mineralization: TheInternational journal of molecular sciences · 2026Article
- Review
- Phosphocitrate Is Superior to Pyrophosphate in Preventing Soft Connective Tissue Calcification in a Mouse Model of Pseudoxanthoma Elasticum.bioRxiv : the preprint server for biology · 2026Article
- High-dose oral pyrophosphate inhibits connective tissue calcification in Abcc6 null mice but may affect bone structure.JBMR plus · 2026Article
- Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential.Biomolecules · 2026Review
- Pyrophosphate dysregulation and impaired FGF23/FGFR signaling contributes to impaired matrix mineralization in bone marrow stromal cultures from sickle cell disease mice.Biochemical and biophysical research communications · 2026Article
- Vascular smooth muscle cell metabolic reprogramming and phenotypic remodeling in atherosclerosis.Cell death discovery · 2025Review
- Pyrophosphate Regulates Multilineage Differentiation in Stem Cells From Human Exfoliated Deciduous Teeth.Clinical and experimental dental research · 2025Article
- ABCC6 and ANK regulate extracellular homeostasis of pyrophosphate and citrate and affect mineral deposition in bones and soft connective tissues.bioRxiv : the preprint server for biology · 2025Article
- A genetic map of human metabolism across the allele frequency spectrum.Nature genetics · 2025Article
- Dietary Citrate Restores Age-Related Endothelial Cell Mitochondrial Dysfunction and Alleviates Atherosclerosis.Aging cell · 2025Article
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
- A Fragile Phosphate/Pyrophosphate Balance: From Essential Mineralization to Rare Calcifying Diseases.Current osteoporosis reports · 2025Review
- Transcriptomics and Targeted Metabolomics Reveal That CES1 Ablation in Macrophages Confers a Distinct Inflammatory Phenotype Involving Altered Interleukin-1β, Citrate, and Lipid Levels.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Citrate Transporter Expression and Localization: TheInternational journal of molecular sciences · 2025Article
- Reduced orthodontic tooth movement inJBMR plus · 2025Article
- Oral Citrate Supplementation Mitigates Age-Associated Pathologic Intervertebral Disc Calcification in LG/J Mice.Aging cell · 2025Article
- Predicting substrates for orphan solute carrier proteins using multi-omics datasets.BMC genomics · 2025Article
- Cementum regeneration strategies: Insights from development and periodontal microenvironment.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ankank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate excretion via the urine was substantially reduced in Ankank/ank mice. Citrate was even undetectable in the urine of a human patient lacking functional ANKH. The hydroxyapatite of Ankank/ank mice contained dramatically reduced levels of both, citrate and PPi and displayed diminished strength. Our results show that ANKH is a critical contributor to extracellular citrate and PPi homeostasis and profoundly affects bone matrix composition and, consequently, bone quality.
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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.