{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T13:44:19Z","timestamp":1764510259506,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,2,22]],"date-time":"2005-02-22T00:00:00Z","timestamp":1109030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Medizinische Hochschule Hannover","award":["HiLF 05\/01"],"award-info":[{"award-number":["HiLF 05\/01"]}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dr Mildred Scheel Stiftung","award":["10-2191"],"award-info":[{"award-number":["10-2191"]}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transforming growth factor \u03b2\u20101 (TGF\u03b2\u20101) is a potent inducer of fibrosis and has been shown to be essential for the development of bone marrow fibrosis in an animal model of idiopathic myelofibrosis (IMF). IMF belongs to the Philadelphia chromosome negative chronic myeloproliferative disorders (Ph<jats:sup>\u2212<\/jats:sup> CMPD). Megakaryocytes and platelets have been suggested as the major cellular source of TGF\u03b2\u20101 in IMF. The osteoclastogenesis inhibitory factor osteoprotegerin (OPG) seems to be regulated by TGF\u03b2\u20101 and substantial involvement of OPG expression in the process of osteosclerosis in IMF has recently been suggested. In order to determine TGF\u03b2\u20101 expression in IMF and other Ph<jats:sup>\u2212<\/jats:sup> CMPD, total bone marrow cells as well as laser\u2010microdissected megakaryocytes were quantitatively analysed by real\u2010time RT\u2010PCR. OPG mRNA expression in fibrotic IMF was correlated with TGF\u03b2\u20101 mRNA expression in a case\u2010specific manner. Both OPG and TGF\u03b2\u20101 were detected immunohistochemically in order to delineate cellular origin. When total bone marrow cells were investigated, TGF\u03b2\u20101 mRNA expression was increased in some but not all cases of IMF (<jats:italic>n<\/jats:italic> = 21), with highest values in fibrotic cases. Unexpectedly, increased values were also observed in essential thrombocythaemia (ET, <jats:italic>n<\/jats:italic> = 11) when compared to non\u2010neoplastic haematopoiesis (<jats:italic>n<\/jats:italic> = 38). Megakaryocytes isolated by laser microdissection displayed elevated TGF\u03b2\u20101 mRNA levels in most of the CMPD samples with no significant differences discernible between fibrotic IMF, polycythaemia vera (PV) and ET. TGF\u03b2\u20101 protein was predominantly expressed by the myeloid lineage in Ph<jats:sup>\u2212<\/jats:sup> CMPD and non\u2010neoplastic haematopoiesis, which, however, displayed lower expression. IMF cases with advanced fibrosis concomitantly overexpressed TGF\u03b2\u20101 and OPG. Immunohistochemically, OPG expression was found in different stromal cells and a subfraction of megakaryocytes. In conclusion, enhanced TGF\u03b2\u20101 expression occurs in megakaryocytes as well as myeloid cells in Ph<jats:sup>\u2212<\/jats:sup> CMPD. TGF\u03b2\u20101 may be necessary, but is not sufficient, to induce bone marrow fibrosis in IMF because non\u2010fibrotic Ph<jats:sup>\u2212<\/jats:sup> CMPD entities share this feature with IMF and cannot be discriminated from each other on the basis of TGF\u03b2\u20101 expression. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1744","type":"journal-article","created":{"date-parts":[[2005,2,22]],"date-time":"2005-02-22T11:16:34Z","timestamp":1109070994000},"page":"548-557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Aberrant expression of transforming growth factor \u03b2\u20101 (TGF\u03b2\u20101) per se does not discriminate fibrotic from non\u2010fibrotic chronic myeloproliferative disorders"],"prefix":"10.1002","volume":"205","author":[{"given":"Oliver","family":"Bock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gero","family":"Loch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrika","family":"Schade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"von 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