Nutrient-Dependent Mitochondrial Fission Enhances Osteoblast Function.
bioenergetics
glucose
metabolism
mitochondrial fission
osteoblasts
palmitate
Journal
Nutrients
ISSN: 2072-6643
Titre abrégé: Nutrients
Pays: Switzerland
ID NLM: 101521595
Informations de publication
Date de publication:
08 May 2023
08 May 2023
Historique:
received:
07
04
2023
revised:
05
05
2023
accepted:
05
05
2023
medline:
13
7
2023
pubmed:
11
7
2023
entrez:
11
7
2023
Statut:
epublish
Résumé
The bone synthesizing function of osteoblasts (OBs) is a highly demanding energy process that requires nutrients. However, how nutrient availability affects OBs behavior and bone mineralization remain to be fully understood. MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiological levels of glucose (G; 5.5 mM) alone or with the addition of palmitic acid (G+PA) at different concentrations. Mitochondria morphology and activity were evaluated by fluorescence microscopy, qPCR, and oxygen consumption rate (OCR) measurement, and OBs function was assessed by mineralization assay. The addition of non-lipotoxic levels of 25 μM PA to G increased mineralization in OBs. G+25 μM PA exposure reduced mitochondria size in OBs, which was associated with increased activation of dynamin-related protein 1, a mitochondrial fission protein, enhanced mitochondria OCR and ATP production, and increased expression of oxidative phosphorylation genes. Treatment with Mdivi-1, a putative inhibitor of mitochondrial fission, reduced osteogenesis and mitochondrial respiration in OBs. Our results revealed that OBs function was enhanced in the presence of glucose and PA at 25 μM. This was associated with increased OBs mitochondrial respiration and dynamics. These results suggest a role for nutrient availability in bone physiology and pathophysiology.
Sections du résumé
BACKGROUND
BACKGROUND
The bone synthesizing function of osteoblasts (OBs) is a highly demanding energy process that requires nutrients. However, how nutrient availability affects OBs behavior and bone mineralization remain to be fully understood.
METHODS
METHODS
MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiological levels of glucose (G; 5.5 mM) alone or with the addition of palmitic acid (G+PA) at different concentrations. Mitochondria morphology and activity were evaluated by fluorescence microscopy, qPCR, and oxygen consumption rate (OCR) measurement, and OBs function was assessed by mineralization assay.
RESULTS
RESULTS
The addition of non-lipotoxic levels of 25 μM PA to G increased mineralization in OBs. G+25 μM PA exposure reduced mitochondria size in OBs, which was associated with increased activation of dynamin-related protein 1, a mitochondrial fission protein, enhanced mitochondria OCR and ATP production, and increased expression of oxidative phosphorylation genes. Treatment with Mdivi-1, a putative inhibitor of mitochondrial fission, reduced osteogenesis and mitochondrial respiration in OBs.
CONCLUSIONS
CONCLUSIONS
Our results revealed that OBs function was enhanced in the presence of glucose and PA at 25 μM. This was associated with increased OBs mitochondrial respiration and dynamics. These results suggest a role for nutrient availability in bone physiology and pathophysiology.
Identifiants
pubmed: 37432387
pii: nu15092222
doi: 10.3390/nu15092222
pmc: PMC10181360
pii:
doi:
Substances chimiques
3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone
0
Glucose
IY9XDZ35W2
Mitochondrial Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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