{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:25:10Z","timestamp":1792009510711,"version":"4.4.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vitamin K is essential for the \u03b3-carboxylation of Gla-containing bone proteins such as osteocalcin and a suboptimal vitamin K status has been linked to osteoporosis but nothing is known of how the lipoprotein-borne vitamin accesses the bone matrix. We have studied the mechanism of transport of lipoproteins labeled with [3H]-phylloquinone (vitamin K1 [K1]) into osteoblasts using both tumor-derived cell lines and normal osteoblast-rich cell populations. We also investigated the effect of heparin in this model since long-term heparin treatment causes osteopenia and the anticoagulant is known to impair normal lipoprotein metabolism. Heparinase treatment, which removes heparan sulfate proteoglycans (HSPG), reduced uptake of [3H]-K1 from triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL). The effect of heparin in this model was complex depending on cell type, concentration, and time but, overall, the results were consistent with an inhibition of vitamin K uptake by osteoblasts. Anti-apolipoprotein E (apoE) antiserum reduced uptake of TRL-[3H]-K1 by 55 \u00b1 4% and LDL-[3H]-K1 uptake by 35 \u00b1 2%. Exogenous apoE4 increased uptake of TRL-[3H]-K1 by 90 \u00b1 1% compared with 53 \u00b1 11% for apoE3 and 52 \u00b1 5% for apoE2. Our findings show that HSPG on the cell surface and apoE in the lipoprotein particles contribute to lipoprotein-K1 uptake by osteoblasts as is known for lipoprotein uptake by hepatocytes. This mechanism is significant in view of the epidemiological association of both undercarboxylation of osteocalcin and the presence of an apo\u03f54 allele with increased fracture risk and reduced bone mineral density (BMD). The inhibition by heparin of lipoprotein-mediated carriage of vitamin K and possibly other lipids to bone may provide a basis for the future understanding of heparin-induced osteoporosis.<\/jats:p>","DOI":"10.1359\/jbmr.2002.17.3.426","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T05:08:32Z","timestamp":1146114512000},"page":"426-433","source":"Crossref","is-referenced-by-count":57,"title":["The Uptake of Lipoprotein-Borne Phylloquinone (Vitamin K1) by Osteoblasts and Osteoblast-Like Cells: Role of Heparan Sulfate Proteoglycans and Apolipoprotein E"],"prefix":"10.1093","volume":"17","author":[{"given":"Paul","family":"Newman","sequence":"first","affiliation":[{"name":"Present address: Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Charlestown, Massachusetts, USA"},{"name":"The Haemophilia Centre, St. Thomas's Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Bonello","sequence":"additional","affiliation":[{"name":"The Haemophilia Centre, St. Thomas's Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S.","family":"Wierzbicki","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, St. Thomas's Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lumb","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, St. Thomas's Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey F.","family":"Savidge","sequence":"additional","affiliation":[{"name":"The Haemophilia Centre, St. Thomas's Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Shearer","sequence":"additional","affiliation":[{"name":"The Haemophilia Centre, St. Thomas's Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019101905400_bib1","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1073\/pnas.71.7.2730","article-title":"Vitamin K dependent modifications of glutamic acid residues in prothrombin","volume":"71","author":"Stenflo","year":"1974","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019101905400_bib2","doi-asserted-by":"crossref","first-page":"6347","DOI":"10.1016\/S0021-9258(19)42259-X","article-title":"The mode of action of vitamin K. 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