4.7 Article

Mtu1 defects are correlated with reduced osteogenic differentiation

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CELL DEATH & DISEASE
卷 12, 期 1, 页码 -

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DOI: 10.1038/s41419-020-03345-5

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  1. National Key Research and Development Program of China [2020YFA0113003, 2018YFC1004803]
  2. Natural Science Foundation of China [31671305]
  3. Fundamental Research Funds for the Central Universities

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Mitochondrial dynamics and function regulation are crucial for successful MSC differentiation. Research showed that Mtu1 defects are linked to reduced osteogenic differentiation by affecting tRNA modifications and ATP production. Mtu1-deficient mice exhibited evident osteopenia.
Accumulating evidence has revealed that mitochondria dynamics and function regulation is essential for the successful mesenchymal stem cell (MSC) differentiation. In the present study, the researchers reported for the first time that Mtu1 defects are correlated with reduced osteogenic differentiation. Using in vitro cultured bone marrow MSCs and stromal cell line MS5, we demonstrated that depressed Mtu1 expression was associated with reduced 2-thiouridine modification of the U34 of mitochondrial tRNA(Gln), tRNA(Glu), and tRNA(Lys), which led to respiratory deficiencies and reduced mitochondrial ATP production, and finally suppressed osteogenic differentiation. As expected, these Mtu1-deficient mice exhibited obvious osteopenia. Therefore, our findings in this study provide new insights into the pathophysiology of osteopenia.

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