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Abstract
In childhood, skeletal growth is driven by transient expansion of
cartilage in the growth plate. The common belief is that energy
production in this hypoxic tissue mainly relies on anaerobic glycolysis
and not on mitochondrial respiratory chain (RC) activity. However,
children with mitochondrial diseases causing RC dysfunction often
present with short stature, which indicates that RC activity may be
essential for cartilage-mediated skeletal growth. To elucidate the role
of the mitochondrial RC in cartilage growth and pathology, we generated
mice with impaired RC function in cartilage. These mice develop normally
until birth, but their later growth is retarded. A detailed molecular
analysis revealed that metabolic signaling and extracellular matrix
formation is disturbed and induces cell death at the cartilage–bone
junction to cause a chondrodysplasia-like phenotype. Hence, the results
demonstrate the overall importance of the metabolic switch from fetal
glycolysis to postnatal RC activation in growth plate cartilage and
explain why RC dysfunction can cause short stature in children with
mitochondrial diseases.
Originalsprache | Englisch |
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Zeitschrift | The Journal of cell biology |
Jahrgang | 218 |
Ausgabenummer | 6 |
Seiten (von - bis) | 1853-1870 |
Seitenumfang | 18 |
ISSN | 0021-9525 |
DOIs | |
Publikationsstatus | Veröffentlicht - 06.2019 |
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DFG - Aufklärung neuer Pathomechanismen von Knochen- und Knorpelerkrankungen
Niehoff, A. & Wirth, B.
01.06.19 → 30.06.23
Projekt: Finanziert durch Drittmittel