{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:26:32Z","timestamp":1784697992469,"version":"3.55.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["CRC\/TRR 205"],"award-info":[{"award-number":["CRC\/TRR 205"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,24]]},"abstract":"<jats:p>\n                    Patients with the renal phosphate\u2013wasting disease X-linked hypophosphatemia (XLH) and\n                    <jats:italic>Hyp<\/jats:italic>\n                    mice, the murine homolog of XLH, are characterized by loss-of-function mutations in phosphate-regulating endopeptidase homolog X-linked (\n                    <jats:italic>PHEX<\/jats:italic>\n                    ), leading to excessive secretion of the bone-derived phosphotropic hormone FGF23. The mineralization defect in patients with XLH and\n                    <jats:italic>Hyp<\/jats:italic>\n                    mice is caused by a combination of hypophosphatemia and local accumulation of mineralization-inhibiting molecules in bone. However, the mechanism by which PHEX deficiency regulates bone cell metabolism remains elusive. Here, we used spatial metabolomics by employing matrix-assisted laser desorption\/ionization (MALDI) Fourier-transform ion cyclotron resonance mass spectrometry imaging (MSI) of undecalcified bone cryosections to characterize in situ metabolic changes in bones of\n                    <jats:italic>Hyp<\/jats:italic>\n                    mice in a holistic, unbiased manner. We found complex changes in\n                    <jats:italic>Hyp<\/jats:italic>\n                    bone metabolism, including perturbations in pentose phosphate, purine, pyrimidine, and phospholipid metabolism. Importantly, our study identified an upregulation of several biochemical pathways involved in intra- and extracellular production of the mineralization inhibitor pyrophosphate in the bone matrix of\n                    <jats:italic>Hyp<\/jats:italic>\n                    mice. Our data emphasize the utility of MSI\u2013based spatial metabolomics in bone research and provide holistic in situ insights as to how Phex deficiency\u2013induced changes in biochemical pathways in bone cells are linked to impaired bone mineralization.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.162138","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T14:00:56Z","timestamp":1666533656000},"source":"Crossref","is-referenced-by-count":12,"title":["Spatial metabolomics reveals upregulation of several pyrophosphate-producing pathways in cortical bone of Hyp mice"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9135-9032","authenticated-orcid":true,"given":"Achim","family":"Buck","sequence":"first","affiliation":[{"name":"Research Unit Analytical Pathology, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6387-3982","authenticated-orcid":true,"given":"Verena M.","family":"Prade","sequence":"additional","affiliation":[{"name":"Research Unit Analytical Pathology, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kunzke","sequence":"additional","affiliation":[{"name":"Research Unit Analytical Pathology, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0801-6958","authenticated-orcid":true,"given":"Reinhold G.","family":"Erben","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, 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