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PMID:22771375

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Citation

Yang, S and Wang, C (2012) The intraflagellar transport protein IFT80 is required for cilia formation and osteogenesis. Bone 51:407-17

Abstract

Intraflagellar transport (IFT) proteins are essential for the assembly and maintenance of cilia, which play important roles in development and homeostasis. IFT80 is a newly defined IFT protein. Partial mutation of IFT80 in humans causes diseases such as Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III with abnormal skeletal development. However, the role and mechanism of IFT80 in osteogenesis is unknown. Here, we first detected IFT80 expression pattern and found that IFT80 was highly expressed in mouse long bone, skull, and during osteoblast differentiation. By using lentivirus-mediated RNA interference (RNAi) technology to silence IFT80 in murine mesenchymal progenitor cell line-C3H10T1/2 and bone marrow derived stromal cells, we found that silencing IFT80 led to either shortening or loss of cilia and the decrease of Arl13b expression - a small GTPase that is localized in cilia. Additionally, silencing IFT80 blocked the expression of osteoblast markers and significantly inhibited ALP activity and cell mineralization. We further found that IFT80 silencing inhibited the expression of Gli2, a critical transcriptional factor in the hedgehog signaling pathway. Overexpression of Gli2 rescued the deficiency of osteoblast differentiation from IFT80-silenced cells, and dramatically promoted osteoblast differentiation. Moreover, introduction of Smo agonist (SAG) promotes osteoblast differentiation, which was partially inhibited by IFT80 silencing. Thus, these results suggested that IFT80 plays an important role in osteogenesis through regulating Hedgehog/Gli signal pathways.

Links

PubMed PMC3412883 Online version:10.1016/j.bone.2012.06.021

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:IFT80

acts_upstream_of_or_within

GO:0001649: osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFT80

acts_upstream_of_or_within

GO:0001649: osteoblast differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95728

P

Seeded From UniProt

complete

MOUSE:IFT80

acts_upstream_of_or_within

GO:1905515: non-motile cilium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GLI2

acts_upstream_of_or_within

GO:0001649: osteoblast differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1915509

P

Seeded From UniProt

complete


See also

References

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