Involvement of mitochondrial biogenesis during the differentiation of human periosteum-derived mesenchymal stem cells into adipocytes, chondrocytes and osteocytes

Lee, A. Ram; Moon, Dong Kyu; Siregar, Adrian S.; Moon, Sun Young; Jeon, Ryoung-Hoon; Son, Young-Bum; Kim, Bo Gyu; Hah, Young‐Sool; Hwang, Sun‐Chul; Byun, June‐Ho; Woo, Dong Kyun

doi:10.1007/s12272-019-01198-x

“…Glycolytic metabolism is known as the main metabolism for self-renewal and maintenance in proliferating stem cells. However, when stem cells commit to differentiate, glycolytic metabolism is shifted to mitochondrial OXPHOS to meet an increased cellular energy demand in differentiated cells [18,19]. OXPHOS occurs within the mitochondria where the mitochondrial respiratory complexes and the ATP synthase produce ATP.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Moon

¹

,

Kim

²

,

Lee

³

et al. 2020

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Background: Osteoporosis is a metabolic bone disorder that leads to low bone mass and microstructural deterioration of bone tissue and increases bone fractures. Resveratrol, a natural polyphenol compound, has pleiotropic effects including anti-oxidative, anti-aging, and anti-cancer effects. Resveratrol also has roles in increasing osteogenesis and in upregulating mitochondrial biogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is still unclear that resveratrol can enhance osteogenic differentiation or mitochondrial biogenesis of periosteum-derived MSCs (PO-MSCs), which play key roles in bone tissue maintenance and fracture healing. Thus, in order to test a possible preventive or therapeutic effect of resveratrol on osteoporosis, this study investigated the effects of resveratrol treatments on osteogenic differentiation and mitochondrial biogenesis of PO-MSCs. Methods: The optimal doses of resveratrol treatment on PO-MSCs were determined by cell proliferation and viability assays. Osteogenic differentiation of PO-MSCs under resveratrol treatment was assessed by alkaline phosphatase activities (ALP, an early biomarker of osteogenesis) as well as by extracellular calcium deposit levels (a late biomarker). Mitochondrial biogenesis during osteogenic differentiation of PO-MSCs was measured by quantifying both mitochondrial mass and mitochondrial DNA (mtDNA) contents.

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“…PO-MSCs were then isolated as described previously (19). Briefly, periosteal explants were harvested from mandibles during surgical extraction of impacted lower third molars.…”

Section: Reagents In Vitro Cell Cultures and Osteogenesis Of Human mentioning

confidence: 99%

“…The cell culture medium was changed every 3 days during the isolation period. For osteogenic differentiation, PO-MSCs were cultured using osteogenesis induction medium (OM) which is composed of DMEM, supplemented with 50 μg/mL Lascorbic acid 2-phosphate, 10 nM dexamethasone, and 10 mM β-glycerophosphate (19).…”

Section: Reagents In Vitro Cell Cultures and Osteogenesis Of Human mentioning

confidence: 99%

“…For mtDNA copy number analysis, total cellular DNA was extracted from cultured PO-MSCs. A quantitative real-time PCR method was used to determine the relative abundance of mtDNA versus nuclear 18S rDNA using corresponding mitochondrial and nuclear PCR primer sets in two parallel PCR reactions as described previously (19). Relative mtDNA copy number was calculated as the ratio of the amount of amplification obtained with mtDNA versus nuclear 18S rDNA PCR primer sets for each…”

Section: Mtdna Copy Number Analysis By Quantitative Pcrmentioning

confidence: 99%

“…Glycolytic metabolism is known as the main metabolism for self-renewal and maintenance in proliferating stem cells. However, when stem cells commit to differentiate, glycolytic metabolism is shifted to mitochondrial OXPHOS to meet an increased cellular energy demand in differentiated cells (18,19). OXPHOS occurs within mitochondria where the mitochondrial respiratory complexes and the ATP synthase produce ATP.…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Moon

¹

,

Kim

²

,

Lee

³

et al. 2020

Preprint

Self Cite

0

View full text Add to dashboard Cite

Background: Osteoporosis is a metabolic bone disorder that leads to low bone mass and microstructural deterioration of bone tissue and increases bone fractures. Resveratrol, a natural polyphenol compound, has pleiotropic effects including anti-oxidative, anti-aging, and anti-cancer effects. Resveratrol also has roles in increasing osteogenesis and in up-regulating mitochondrial biogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is still unclear that resveratrol can enhance osteogenic differentiation or mitochondrial biogenesis of periosteum-derived MSCs (PO-MSCs), which play key roles in bone tissue maintenance and fracture healing. Thus, in order to test a possible preventive or therapeutic effect of resveratrol on osteoporosis, this study investigated effects of resveratrol treatments on osteogenic differentiation and mitochondrial biogenesis of PO-MSCs.Methods: The optimal doses of resveratrol treatment on PO-MSCs were determined by cell proliferation and viability assays. Osteogenic differentiation of PO-MSCs under resveratrol treatment was assessed by alkaline phosphatase activities (ALP, an early biomarker of osteogenesis) as well as by extracellular calcium deposit levels (a late biomarker). Mitochondrial biogenesis during osteogenic differentiation of PO-MSCs was measured by quantifying both mitochondrial mass and mitochondrial DNA (mtDNA) contents.Results: Resveratrol treatments above 10 µM seem to have negative effects on cell proliferation and viability of PO-MSCs. Resveratrol treatment (at 5 µM) on PO-MSCs during osteogenic differentiation increased both ALP activities and calcium deposits compared to untreated control groups, demonstrating an enhancing effect of resveratrol on osteogenesis. In addition, resveratrol treatment (at 5 µM) during osteogenic differentiation of PO-MSCs increased both mitochondrial mass and mtDNA copy numbers, indicating that resveratrol can bolster mitochondrial biogenesis in the process of PO-MSC osteogenic differentiation.Conclusion: Taken together, the findings of this study describe roles of resveratrol in promoting osteogenesis and mitochondrial biogenesis of human PO-MSCs suggesting a possible application of resveratrol as a supplement for osteoporosis and/or osteoporotic fractures.

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Role of the Mitochondrial Permeability Transition in Bone Metabolism and Aging

Sautchuk

¹

,

Chen

²

,

McArthur

³

et al. 2020

Journal of Bone and Mineral Research

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The mitochondrial permeability transition pore (MPTP) and its positive regulator, cyclophilin D (CypD), play important pathophysiological roles in aging. In bone tissue, higher CypD expression and pore activity are found in aging; however, a causal relationship between CypD/MPTP and bone degeneration needs to be established. We previously reported that CypD expression and MPTP activity are downregulated during osteoblast (OB) differentiation and that manipulations in CypD expression affect OB differentiation and function. Using a newly developed OB‐specific CypD/MPTP gain‐of‐function (GOF) mouse model, we here present evidence that overexpression of a constitutively active K166Q mutant of CypD (caCypD) impairs OB energy metabolism and function, and bone morphological and biomechanical parameters. Specifically, in a spatial‐dependent and sex‐dependent manner, OB‐specific CypD GOF led to a decrease in oxidative phosphorylation (OxPhos) levels, higher oxidative stress, and general metabolic adaptations coincident with the decreased bone organic matrix content in long bones. Interestingly, accelerated bone degeneration was present in vertebral bones regardless of sex. Overall, our work confirms CypD/MPTP overactivation as an important pathophysiological mechanism leading to bone degeneration and fragility in aging. © 2023 American Society for Bone and Mineral Research (ASBMR).

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Involvement of mitochondrial biogenesis during the differentiation of human periosteum-derived mesenchymal stem cells into adipocytes, chondrocytes and osteocytes

Cited by 20 publications

References 44 publications

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Role of the Mitochondrial Permeability Transition in Bone Metabolism and Aging

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