{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:04:57Z","timestamp":1758398697673,"version":"3.41.2"},"reference-count":41,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2021YFC2501700"],"award-info":[{"award-number":["2021YFC2501700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["7242106"],"award-info":[{"award-number":["7242106"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Fund","award":["82200993","82100942","82270938"],"award-info":[{"award-number":["82200993","82100942","82270938"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-002"],"award-info":[{"award-number":["2021-I2M-1-002"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-D-006","2022-PUMCH-B-014","2022-PUMCH-A-202"],"award-info":[{"award-number":["2022-PUMCH-D-006","2022-PUMCH-B-014","2022-PUMCH-A-202"]}]},{"name":"Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences","award":["2023-PT320-10"],"award-info":[{"award-number":["2023-PT320-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder characterized by skeletal and skin abnormalities. Genetic defects in prostaglandin E2 (PGE2) metabolism are known to cause PHO. However, the global impact and clinical significance of eicosanoids and oxylipins beyond PGE2 remain to be elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study aimed to investigate oxylipin networks in PHO, including the 2 subtypes, PHOAR1 and PHOAR2, and examine their associations with clinical characteristics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a targeted metabolomic study involving 16 patients with PHO and 16 age- and sex-matched healthy controls. Serum samples were collected at the time of diagnosis. Metabolites were quantified using ultra-high\u2013performance liquid chromatography-tandem mass spectrometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Laboratory analyses confirmed elevated levels of PGE2 in patients with PHO, consistent with the established pathogenesis. About 60 oxidized lipid metabolites were identified, with 19 differentially expressed in PHO. Besides the COX\/PGE2 pathway, the lipoxygenase-mediated pathway was also involved in PHO. The metabolites 5-OxoETE, 15-OxoETE, 8S,15S-DiHETE, PGE2, 11\u03b2-PGE2, PGB2, LTB4, and LTE4 were significantly altered. Correlation analyses revealed associations between oxylipin metabolites and clinical features, including bone microarchitecture. Notably, the study highlighted differences in the oxylipin metabolite profiles between patients with PHOAR1 and patients with PHOAR2, suggesting distinct metabolic signatures for each subtype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study indicated a significant perturbation in oxylipin metabolism among patients with PHO, with distinct metabolic signatures observed between PHOAR1 and PHOAR2. The disruption extended beyond the metabolism of PGE2. It encompassed a broader alteration across the polyunsaturated fatty acid metabolism spectrum, including various eicosanoids and oxylipins. Our work provided a comprehensive understanding of the pathogenesis of PHO, and underscored the potential for subtype-specific therapeutic interventions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae737","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T11:54:04Z","timestamp":1732794844000},"page":"e2591-e2604","source":"Crossref","is-referenced-by-count":2,"title":["Targeting Metabolomics in Primary Hypertrophic Osteoarthropathy: Uncovering Novel Insights into Disease Pathogenesis"],"prefix":"10.1210","volume":"110","author":[{"given":"Qianqian","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science , Beijing 100730 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,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-8789","authenticated-orcid":false,"given":"Ou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science , Beijing 100730 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2252","authenticated-orcid":false,"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science , Beijing 100730 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