{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:22:42Z","timestamp":1773285762245,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,5,12]],"date-time":"2010-05-12T00:00:00Z","timestamp":1273622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The receptor activator of nuclear factor\u2010kappaB ligand (RANKL) and interleukin\u20101beta are osteoclast activating factors which are abnormally expressed in bone marrow stromal cells and plasma cells of multiple myeloma patients. In this work we analyzed RANKL expression in human bone marrow mesenchymal stromal cells and the effect of the bisphosphonate ibandronate on RANKL expression after IL\u20101beta activation of ERK pathway. Mesenchymal stromal cells were obtained from bone marrow iliac aspirates from multiple myeloma patients at stages II\/III and non\u2010osteoporotics control donors; these cells were maintained under long\u2010term culture conditions. Cells were cultured in the presence or the absence of 5\u2009ng\/ml IL\u20101beta and\/or 5\u2009\u00b5M ibandronate, during selected periods. mRNA for RANKL and protein levels were assayed by RT\u2010PCR and Western blot, respectively. Human bone marrow stromal cell line HS\u20105 was used for assessing IL 1beta\u2010 and ibandronate\u2010ERK phosphorylation responses. Multiple myeloma mesenchymal stromal cells differentiate from control cells by increased basal RANKL expression. IL\u20101beta up regulated RANKL expression showed dependent on activated MEK\/ERK pathway. Finally, the bisphosphonate ibandronate, that hindered activation of the MEK\/ERK pathway significantly inhibited both basal and IL\u20101beta dependent RANKL expression by cells. Results indicate that RANKL expression involves the MEK\/ERK pathway in multiple myeloma mesenchymal stromal cells, and that early obstruction of this path, such as that achieved with ibandronate, significantly deters RANKL protein expression. J. Cell. Biochem. 111: 130\u2013137, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22676","type":"journal-article","created":{"date-parts":[[2010,5,12]],"date-time":"2010-05-12T17:40:38Z","timestamp":1273686038000},"page":"130-137","source":"Crossref","is-referenced-by-count":10,"title":["The increased expression of receptor activator of nuclear\u2010\u03baB ligand (RANKL) of multiple myeloma bone marrow stromal cells is inhibited by the bisphosphonate ibandronate"],"prefix":"10.1002","volume":"111","author":[{"given":"Mireya","family":"Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M","family":"Pino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Figueroa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan 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