Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse
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Authors
Gaur, TriptiHussain, Sadiq
Mudhasani, Rajini R.
Parulkar, Isha
Colby, Jennifer L.
Frederick, Dana
Kream, Barbara E.
Van Wijnen, Andre J.
Stein, Janet L.
Stein, Gary S.
Jones, Stephen N.
Lian, Jane B.
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2010-04-01Keywords
AnimalsCell Aging
*Cell Differentiation
Collagen Type I
DEAD-box RNA Helicases
Embryo, Mammalian
Endoribonucleases
Genes, Lethal
Mice
Mice, Inbred Strains
Osteoblasts
Osteogenesis
RNA, Messenger
Stem Cells
Cell Biology
Metadata
Show full item recordAbstract
MicroRNA attenuation of protein translation has emerged as an important regulator of mesenchymal cell differentiation into the osteoblast lineage. A compelling question is the extent to which miR biogenesis is obligatory for bone formation. Here we show conditional deletion of the Dicer enzyme in osteoprogenitors by Col1a1-Cre compromised fetal survival after E14.5. A mechanism was associated with the post-commitment stage of osteoblastogenesis, demonstrated by impaired ECM mineralization and reduced expression of mature osteoblast markers during differentiation of mesenchymal cells of ex vivo deleted Dicer(c/c). In contrast, in vivo excision of Dicer by Osteocalcin-Cre in mature osteoblasts generated a viable mouse with a perinatal phenotype of delayed bone mineralization which was resolved by 1 month. However, a second phenotype of significantly increased bone mass developed by 2 months, which continued up to 8 months in long bones and vertebrae, but not calvariae. Cortical bone width and trabecular thickness in Dicer(Deltaoc/Deltaoc) was twice that of Dicer(c/c) controls. Normal cell and tissue organization was observed. Expression of osteoblast and osteoclast markers demonstrated increased coupled activity of both cell types. We propose that Dicer generated miRs are essential for two periods of bone formation, to promote osteoblast differentiation before birth, and control bone accrual in the adult.Source
Dev Biol. 2010 Apr 1;340(1):10-21. Epub 2010 Jan 15. Link to article on publisher's siteDOI
10.1016/j.ydbio.2010.01.008Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36034Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.ydbio.2010.01.008