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Synthesis of osteoprotegerin and RANKL by megakaryocytes is modulated by oestrogen
Author(s) -
Bord S.,
Frith E.,
Ireland D. C.,
Scott M. A.,
Craig J. I. O.,
Compston J. E.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05024.x
Subject(s) - rankl , osteoprotegerin , megakaryocytopoiesis , endocrinology , medicine , receptor , immunocytochemistry , chemistry , activator (genetics) , rank ligand , megakaryocyte , biology , haematopoiesis , microbiology and biotechnology , stem cell
Summary To investigate the mechanisms by which megakaryocytes (MKs) may influence bone remodelling, CD34 + cells were cultured for 6, 9 and 12 d with or without 17 β ‐oestradiol (E) and immunolocalized for osteoprotegerin (OPG), receptor activator of nuclear factor (NF)‐ κ B ligand (RANKL) and CD61. Specific protein expression was measured quantitatively by image analysis. Fluorescence‐based immunocytochemistry was used to co‐localize OPG and RANKL with CD61. OPG and RANKL mRNA was assessed in CD61 + cells with or without E at 24 and 48 h. At 6 d, OPG and RANKL expression was unchanged by E treatment. At 9 d, the E‐treated cultures with maturing MKs showed a 1·72‐fold ( P < 0·01) increase in OPG expression and a 1·8‐fold ( P < 0·01) reduction in RANKL. Maximal OPG expression was seen at 12 d with a threefold induction of expression ( P < 0·001), whilst RANKL levels were further suppressed by 2·3‐fold compared with controls ( P < 0·001). CD61 co‐localized with OPG and RANKL. mRNA data were consistent with that of protein, with a 90‐fold induction in OPG expression and a 34‐fold suppression of RANKL expression by E ( P < 0·001). Thus, E stimulates megakaryocytopoiesis and modulates OPG and RANKL expression, providing evidence that MKs may play a role in bone remodelling and, in particular, in E‐induced changes in osteoclastogenesis and bone resorption.