Back to Search
Start Over
Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response
Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Heterotopic ossification (HO) is a pathological condition characterized by the deposition of mineralized tissue in ectopic locations such as the skeletal muscle. The precise cellular origin and molecular mechanisms underlying HO are still debated. In our study we focus on the differentiation of mesoangioblasts (MABs), a population of multipotent skeletal muscle precursors. High-content screening for small molecules that perturb MAB differentiation decisions identified Idoxuridine (IdU), an antiviral and radiotherapy adjuvant, as a molecule that promotes MAB osteogenic differentiation while inhibiting myogenesis. IdU-dependent osteogenesis does not rely on the canonical BMP-2/SMADs osteogenic pathway. At pro-osteogenic conditions IdU induces a mild DNA Damage Response (DDR) that activates ATM and p38 eventually promoting the phosphorylation of the osteogenesis master regulator RUNX2. By interfering with this pathway IdU-induced osteogenesis is severely impaired. Overall, our study suggests that induction of the DDR promotes osteogenesis in muscle resident MABs thereby offering a new mechanism that may be involved in the ectopic deposition of mineralized tissue in the muscle.
- Subjects :
- 0301 basic medicine
DNA damage
p38 mitogen-activated protein kinases
Population
lcsh:Medicine
Bone Morphogenetic Protein 2
Core Binding Factor Alpha 1 Subunit
Smad Proteins
Article
03 medical and health sciences
0302 clinical medicine
Osteogenesis
DNA damage skeletal muscle
Idoxuridine
medicine
Animals
Progenitor cell
lcsh:Science
Muscle, Skeletal
education
education.field_of_study
Multidisciplinary
Settore BIO/18
Chemistry
Myogenesis
Multipotent Stem Cells
Ossification, Heterotopic
lcsh:R
Skeletal muscle
Cell Differentiation
3. Good health
Cell biology
RUNX2
030104 developmental biology
medicine.anatomical_structure
Phosphorylation
lcsh:Q
030217 neurology & neurosurgery
DNA Damage
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....712d96b9763a63a226adf8fdecbfe732
- Full Text :
- https://doi.org/10.1038/s41598-019-41926-3