{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:34:55Z","timestamp":1781768095455,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"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":"publisher","award":["BE 4169\/8\u20102"],"award-info":[{"award-number":["BE 4169\/8\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Posttraumatic osteomyelitis and the ensuing bone defects are a debilitating complication after open fractures with little therapeutic options. We have recently identified potent osteoanabolic effects of sphingosine\u20101\u2010phosphate (S1P) signalling and have now tested whether it may beneficially affect bone regeneration after infection. We employed pharmacological S1P lyase inhibition by 4\u2010deoxypyrodoxin (DOP) to raise S1P levels in vivo in an unicortical long bone defect model of posttraumatic osteomyelitis in mice. In a translational approach, human bone specimens of clinical osteomyelitis patients were treated in organ culture in vitro with DOP. Bone regeneration was assessed by \u03bcCT, histomorphometry, immunohistology and gene expression analysis. The role of S1P receptors was addressed using S1PR3 deficient mice. Here, we present data that DOP treatment markedly enhanced osteogenesis in posttraumatic osteomyelitis. This was accompanied by greatly improved osteoblastogenesis and enhanced angiogenesis in the callus accompanied by osteoclast\u2010mediated bone remodelling. We also identified the target of increased S1P to be the S1PR3 as S1PR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed no improvement of bone regeneration by DOP. In the human bone explants, bone mass significantly increased along with enhanced osteoblastogenesis and angiogenesis. Our data suggest that enhancement of S1P\/S1PR3 signalling may be a promising therapeutic target for bone regeneration in posttraumatic osteomyelitis.<\/jats:p>","DOI":"10.1111\/jcmm.17952","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T05:06:35Z","timestamp":1694754395000},"page":"3786-3795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological elevation of sphingosine\u20101\u2010phosphate by <scp>S1P<\/scp> lyase inhibition accelerates bone regeneration after post\u2010traumatic osteomyelitis"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-4290","authenticated-orcid":false,"given":"Johannes M.","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"},{"name":"Department of Trauma Surgery and General Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalena","family":"Wille","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine III University Hospital D\u00fcsseldorf and Heinrich Heine Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fueth","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Weske","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine III University Hospital D\u00fcsseldorf and Heinrich Heine Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Lotzien","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and General Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Reinkemeier","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wallner","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Sogorski","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Dittfeld","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Becerikli","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Schildhauer","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery and General Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Lehnhardt","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo","family":"Levkau","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine III University Hospital D\u00fcsseldorf and Heinrich Heine Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3480-6956","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Behr","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery BG University Hospital Bergmannsheil Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199072020-00023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(04)16727-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1214158"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.243"},{"issue":"4","key":"e_1_2_10_6_1","first-page":"395","article-title":"Osteomyelitis: diagnosis and treatment","volume":"104","author":"Bury DC","year":"2021","journal-title":"Am Fam Physician"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foot.2010.11.005"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197001222820406"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(03)00292-7"},{"key":"e_1_2_10_10_1","first-page":"1027","article-title":"Diagnosis and management of osteomyelitis","volume":"84","author":"Hatzenbuehler J","year":"2011","journal-title":"Am Fam Physician"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149389"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0158"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23555"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0266"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-020-01924-9"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-021-01269-4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.09.003"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.107.07113"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0005-y"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10037"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020420"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403937200"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38069-5"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003317107"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6215"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.09.003"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.04.008"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1672"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.02.005"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.10.001"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2017.0225"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112437"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/7651_2017_26"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13145"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200339RRR"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.03.017"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2009.0539"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.04.001"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07713"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101474"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.447250"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2015.10.009"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.12.28"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.2147\/jir.S302117"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511411061"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11133584"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.11.001"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-010-1634-8"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0192-0561(99)00088-0"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401842"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T14:44:07Z","timestamp":1706885047000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.17952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":50,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/jcmm.17952"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.17952","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]},"assertion":[{"value":"2023-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}