{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:51:43Z","timestamp":1789055503000,"version":"build-2803163510"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":1152,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":833,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lipids play a crucial role in signaling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesized to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralization. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics. Multivariate analysis identified 96 and 80 lipid ions with differential abundances across joint tissues in juvenile and adult mice, respectively. In both ages, marrow was enriched in phospholipid platelet activating factors (PAFs) and related metabolites, cortical bone had a low lipid content, whereas lysophospholipids were strikingly enriched in the growth plate, an active site of mineralization and PHOSPHO1 activity. Spatially-resolved profiling of PHOSPHO1-knockout (KO) mice across the resting, proliferating, and hypertrophic growth plate zones revealed 272, 306, and 296 significantly upregulated, and 155, 220, and 190 significantly downregulated features, respectively, relative to wild-type (WT) controls. Of note, phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine, and phosphatidylethanolamine derived lipid ions were upregulated in PHOSPHO1-KO versus WT. Our imaging pipeline has established a spatially-resolved lipid signature of joint tissues and has demonstrated that PHOSPHO1 ablation significantly alters the growth plate lipidome, highlighting an essential role of the PHOSPHO1-mediated membrane phospholipid metabolism in lipid and bone homeostasis. \u00a9 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4796","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T02:18:40Z","timestamp":1677205120000},"page":"792-807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Spatial Lipidomic Profiling of Mouse Joint Tissue Demonstrates the Essential Role of PHOSPHO1 in Growth Plate Homeostasis"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-716X","authenticated-orcid":false,"given":"Jordan","family":"Tzvetkov","sequence":"first","affiliation":[{"name":"York Biomedical Research Institute and Department of Biology University of York York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A.","family":"Stephen","sequence":"additional","affiliation":[{"name":"The Roslin Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-8009","authenticated-orcid":false,"given":"Scott","family":"Dillon","sequence":"additional","affiliation":[{"name":"Wellcome-Medical Research Council (MRC) Cambridge Stem Cell Institute University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-2671","authenticated-orcid":false,"given":"Jose Luis","family":"Millan","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys, Medical Discovery Institute La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-1984","authenticated-orcid":false,"given":"Anke J.","family":"Roelofs","sequence":"additional","affiliation":[{"name":"Centre for Arthritis and Musculoskeletal Health University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-862X","authenticated-orcid":false,"given":"Cosimo","family":"De Bari","sequence":"additional","affiliation":[{"name":"Centre for Arthritis and Musculoskeletal Health University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4970-4039","authenticated-orcid":false,"given":"Colin","family":"Farquharson","sequence":"additional","affiliation":[{"name":"The Roslin Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1337-3482","authenticated-orcid":false,"given":"Tony","family":"Larson","sequence":"additional","affiliation":[{"name":"York Biomedical Research Institute and Department of Biology University of York York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5730-8976","authenticated-orcid":false,"given":"Paul","family":"Genever","sequence":"additional","affiliation":[{"name":"York Biomedical Research Institute and Department of Biology University of York York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"issue":"7797","key":"2024012714101711500_jbmr4796-bib-0001","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41586-020-2050-1","article-title":"Lipid availability determines fate of skeletal progenitor cells via SOX9","volume":"579","author":"van Gastel","year":"2020","journal-title":"Nature"},{"key":"2024012714101711500_jbmr4796-bib-0002","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/bonekey.2015.82","article-title":"The regulation of osteoclast differentiation by Wnt 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