{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:03:58Z","timestamp":1762671838384},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T00:00:00Z","timestamp":1361491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Lytic bone disease (<jats:styled-content style=\"fixed-case\">LBD<\/jats:styled-content>) in multiple myeloma (<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>) is caused by osteoclast hyperactivation and osteoblast inhibition. Based on <jats:italic>in vitro<\/jats:italic> studies, the hepatocyte growth factor (<jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content>) pathway is thought to be central in osteoblast inhibition. We evaluated the gene expression of the <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content> pathway <jats:italic>in vivo<\/jats:italic> using bone marrow biopsies (<jats:styled-content style=\"fixed-case\">BMB<\/jats:styled-content>s) of patients with <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> and monoclonal gammopathy of undetermined significance (<jats:styled-content style=\"fixed-case\">MGUS<\/jats:styled-content>), and healthy volunteers (<jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">BMB<\/jats:styled-content>s (<jats:italic>N<\/jats:italic>\u00a0=\u00a0110) obtained at diagnosis were snap\u2010frozen and used to evaluate gene expression by quantitative reverse transcription polymerase chain reaction. <jats:styled-content style=\"fixed-case\">LBD<\/jats:styled-content> was evaluated using standard radiographs. Enzyme\u2010linked immunosorbent assay (<jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>) was performed on matched bone marrow plasma and immunohistochemistry on matched formalin\u2010fixed paraffin\u2010embedded biopsies. Gene expression of <jats:styled-content style=\"fixed-case\"><jats:italic>HGF<\/jats:italic><\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> <jats:italic>SDC1<\/jats:italic><\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\"><jats:italic>MET<\/jats:italic><\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">BMB<\/jats:styled-content>s were significantly altered in <jats:styled-content style=\"fixed-case\">MM <\/jats:styled-content><jats:italic>versus <\/jats:italic><jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MGUS<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\"><jats:italic>HGF<\/jats:italic><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>MET<\/jats:italic><\/jats:styled-content> correlated with the extent of <jats:styled-content style=\"fixed-case\">LBD<\/jats:styled-content>. A significant correlation between gene and protein expression levels was observed for <jats:styled-content style=\"fixed-case\">SDC<\/jats:styled-content>1 (<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yndecan\u20101) and <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content>. The <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content> bone marrow plasma level was significantly lower in <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> patients with no\/limited <jats:italic>versus<\/jats:italic> advanced <jats:styled-content style=\"fixed-case\">LBD<\/jats:styled-content>. Our novel approach using snap\u2010frozen <jats:styled-content style=\"fixed-case\">BMB<\/jats:styled-content>s seems generally applicable because it allows evaluation of gene expression independent of the extent of <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> plasma\u2010cell infiltration. Our study highlights the importance of the <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content> pathway in <jats:styled-content style=\"fixed-case\">MM LBD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.12270","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T05:54:07Z","timestamp":1361512447000},"page":"373-382","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease"],"prefix":"10.1111","volume":"161","author":[{"given":"Ida B.","family":"Kristensen","sequence":"first","affiliation":[{"name":"Department of Haematology Odense University Hospital Odense Denmark"},{"name":"Institute of Clinical Research University of Southern Denmark Odense Denmark"},{"name":"Department of Cancer and Inflammation research Institute of 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