Back to Search
Start Over
MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle.
MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2006 Nov 07; Vol. 103 (45), pp. 16995-7000. Date of Electronic Publication: 2006 Oct 31. - Publication Year :
- 2006
-
Abstract
- Inflammatory myopathies (IM) are acquired diseases of skeletal muscle comprising dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). Immunosuppressive therapies, usually beneficial for DM and PM, are poorly effective in IBM. We report the isolation and characterization of mesoangioblasts, vessel-associated stem cells, from diagnostic muscle biopsies of IM. The number of cells isolated, proliferation rate and lifespan, markers expression, and ability to differentiate into smooth muscle do not differ among normal and IM mesoangioblasts. At variance with normal, DM and PM mesoangioblasts, cells isolated from IBM, fail to differentiate into skeletal myotubes. These data correlate with lack in connective tissue of IBM muscle of alkaline phosphatase (ALP)-positive cells, conversely dramatically increased in PM and DM. A myogenic inhibitory basic helix-loop-helix factor B3 is highly expressed in IBM mesoangioblasts. Indeed, silencing this gene or overexpressing MyoD rescues the myogenic defect of IBM mesoangioblasts, opening novel cell-based therapeutic strategies for this crippling disorder.
- Subjects :
- Alkaline Phosphatase metabolism
Basic Helix-Loop-Helix Transcription Factors antagonists & inhibitors
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Differentiation
Cells, Cultured
Gene Expression
Gene Silencing
Humans
Muscle Development
Muscle, Skeletal blood supply
Myoblasts, Skeletal metabolism
Myoblasts, Skeletal pathology
Myositis, Inclusion Body therapy
RNA, Small Interfering genetics
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
MyoD Protein genetics
MyoD Protein metabolism
Myositis, Inclusion Body metabolism
Myositis, Inclusion Body pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 103
- Issue :
- 45
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 17077152
- Full Text :
- https://doi.org/10.1073/pnas.0603386103