Inactivation of menin, the product of the XXXX gene, inhibits the commitment of multipotential mesenchymal stem cells into the osteoblast lineage.

@entity7582 @entity129 @entity12097 @entity14901 @entity2447 @entity19 @entity2450 @entity21602 @entity8386 @entity8385
The physiological roles of menin, the product of the @entity7582 gene, are not known. Homozygous menin knockout @entity19 exhibit @entity129 . We, therefore, investigated the role of menin in the regulation of osteoblastic differentiation. Menin antisense oligonucleotides (AS-oligo) reduced endogenous menin expression in the C3H10T1/2 (10T1/2) @entity19 mesenchymal stem cells and antagonized alkaline phosphatase (ALP) activity and the expression of type I collagen, @entity2447 / @entity2447 ( @entity2447 ), and @entity2450 ( @entity2450 ) induced by @entity8385 ( @entity8385 ). AS-oligo did not affect adipogenic markers (Oil red staining and @entity12097 expression) and chondrogenic markers (Alcian blue staining and type IX collagen) induced by @entity8385 in 10T1/2 cells. Menin co-immunoprecipitated with @entity14901 and @entity21602 , and inactivation of menin antagonized @entity8385 -induced transcriptional activity of @entity8386 . In osteoblastic @entity19 cells, AS-oligo affected neither @entity8385 -stimulated ALP activity nor the expression of @entity2447 and @entity2450 . Stable inactivation of menin in @entity19 cells increased ALP activity, mineralization, and the expression of type I collagen and @entity2450 . In 21-day cultures of @entity19 cells and @entity8385 -treated 10T1/2 cells, endogenous menin expression increased up to day 14 and declined thereafter. These data indicate that menin inactivation specifically inhibits the commitment of pluripotent mesenchymal stem cells to the osteoblast lineage, mediated by menin and @entity8386 interactions. Menin is important for both early differentiation of osteoblasts and inhibition of their later differentiation, and it might be crucial for intramembranous ossification.
