The increased expression of receptor activator of nuclear-kappaB ligand (RANKL) of multiple myeloma bone marrow stromal cells is inhibited by the bisphosphonate ibandronate.
J Cell Biochem
; 111(1): 130-7, 2010 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-20506157
The receptor activator of nuclear factor-kappaB ligand (RANKL) and interleukin-1beta 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-1beta activation of ERK pathway. Mesenchymal stromal cells were obtained from bone marrow iliac aspirates from multiple myeloma patients at stages II/III and non-osteoporotics control donors; these cells were maintained under long-term culture conditions. Cells were cultured in the presence or the absence of 5 ng/ml IL-1beta and/or 5 microM ibandronate, during selected periods. mRNA for RANKL and protein levels were assayed by RT-PCR and Western blot, respectively. Human bone marrow stromal cell line HS-5 was used for assessing IL 1beta- and ibandronate-ERK phosphorylation responses. Multiple myeloma mesenchymal stromal cells differentiate from control cells by increased basal RANKL expression. IL-1beta 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-1beta 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
/
Células Estromais
/
Difosfonatos
/
Ligante RANK
/
Mieloma Múltiplo
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos