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A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization.
- Source :
-
Journal of Cell Biology . 7/25/2011, Vol. 194 Issue 2, p277-289. 13p. - Publication Year :
- 2011
-
Abstract
- A deletion mutation called fro (fragilitas ossium) in the murine Smpd3 (sphingomyelin phospho-diesterase 3) gene leads to a severe skeletal dysplasia. Smpd3 encodes a neutral sphingomyelinase (nSMase2), which cleaves sphingomyelin to generate bioactive lipid metabolites. We examined endochondral ossification in embryonic day 15.5 fro/fro mouse embryos and observed impaired apoptosis of hypertrophic chondrocytes and severely undermineralized cortical bones in the developing skeleton. In a recent study, it was suggested that nSMase2 activity in the brain regulates skeletal development through endocrine factors. However , we detected Smpd3 expression in both embryonic and postnatal skeletal tissues in wild-type mice. To investigate whether nSMase2 plays a cell-autonomous role in these tissues, we examined the in vitro mineralization properties of fro/fro osteoblast cultures. fro/fro cultures mineralized less than the control osteoblast cultures. We next generated fro/fro;Col1a1-Smpd3 mice, in which osteoblast-specific expression of Smpd3 corrected the bone abnormalities observed in fro/fro embryos without affecting the cartilage phenotype. Our data suggest tissue-specific roles for nSMase2 in skeletal tissues. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DYSPLASIA
*LIPID metabolism
*EMBRYOS
*APOPTOSIS
*LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 00219525
- Volume :
- 194
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 65072733
- Full Text :
- https://doi.org/10.1083/jcb.201102051