Sostdc1: A soluble BMP and Wnt antagonist that is induced by the interaction between myeloma cells and osteoblast lineage cells.
Bone
; 122: 82-92, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30776499
ABSTRACT
Multiple myeloma (MM) is characterised by destructive lytic bone disease, caused by induction of bone resorption and impaired bone formation. Our understanding of the molecular mechanisms responsible for osteoblast suppression, are limited. Using the 5T2MM murine model of MM we have previously shown that suppression of the activity of a known inhibitor of bone formation Dikkopf-1 (Dkk1) prevents the development of lytic bone disease. Here we have demonstrated that another potential inhibitor of bone formation, sclerostin domain containing 1 (Sostdc1) is expressed at low levels in MM and osteoblast lineage cells when these cells are grown separately in cell culture but its expression is significantly induced in both cell types when these cells are in contact. The distribution of Sostdc1 staining in bones infiltrated with 5TGM1 myeloma cells in vivo suggested its presence in both myeloma and osteoblast lineage populations when in close proximity. We have also shown that recombinant Sostdc1 inhibits both bone morphogenic proteins (BMP2 and 7) and Wnt signalling in primary osteoblasts and suppresses differentiation of these cells. Together, these findings suggest that Sostdc1 expression in 5TGM1-infiltrated bones as a result of the interaction between myeloma and osteoblast lineage populations, could result in suppression of osteoblast differentiation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Comunicação Celular
/
Linhagem da Célula
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Proteínas Morfogenéticas Ósseas
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Wnt
/
Mieloma Múltiplo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Bone
Ano de publicação:
2019
Tipo de documento:
Article