Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response

M. Rosina, F. Langone, G. Giuliani, A. Cerquone Perpetuini, A. Reggio, A. Calderone, C. Fuoco, L. Castagnoli, C. Gargioli, G. Cesareni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5447
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Idoxuridine
Osteogenesis
Muscle Cells
DNA Damage
Skeletal Muscle
Stem Cells
Heterotopic Ossification
Choristoma
Muscles
Adjuvant Radiotherapy
Muscle Development
Antiviral Agents
Phosphorylation
Population

ASJC Scopus subject areas

  • General

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Rosina, M., Langone, F., Giuliani, G., Cerquone Perpetuini, A., Reggio, A., Calderone, A., ... Cesareni, G. (2019). Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response. Scientific Reports, 9(1), [5447]. https://doi.org/10.1038/s41598-019-41926-3

Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response. / Rosina, M.; Langone, F.; Giuliani, G.; Cerquone Perpetuini, A.; Reggio, A.; Calderone, A.; Fuoco, C.; Castagnoli, L.; Gargioli, C.; Cesareni, G.

In: Scientific Reports, Vol. 9, No. 1, 5447, 01.12.2019.

Research output: Contribution to journalArticle

Rosina, M, Langone, F, Giuliani, G, Cerquone Perpetuini, A, Reggio, A, Calderone, A, Fuoco, C, Castagnoli, L, Gargioli, C & Cesareni, G 2019, 'Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response', Scientific Reports, vol. 9, no. 1, 5447. https://doi.org/10.1038/s41598-019-41926-3
Rosina M, Langone F, Giuliani G, Cerquone Perpetuini A, Reggio A, Calderone A et al. Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response. Scientific Reports. 2019 Dec 1;9(1). 5447. https://doi.org/10.1038/s41598-019-41926-3
Rosina, M. ; Langone, F. ; Giuliani, G. ; Cerquone Perpetuini, A. ; Reggio, A. ; Calderone, A. ; Fuoco, C. ; Castagnoli, L. ; Gargioli, C. ; Cesareni, G. / Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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