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

Abstract

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 (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 seems 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 differnetiation 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, this study describes 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.

Mechanical and chemical cues synergistically promote human venous smooth muscle cell osteogenesis through integrin β1‐ERK1/2 signaling: A cell model of hemodialysis fistula calcification

“…This implies an early stage of the osteogenesis process. Our findings are consistent with the increased mitochondrial biogenesis that occurs during osteogenic differentiation of mesenchymal stem cells 35–37 …”

“…It has been reported that mitochondrial biogenesis increases during the osteogenesis process, for example, osteogenic differentiation of mesenchymal stem cells 35–37 . Therefore, we examined the gene expression of mitochondrial transcription factor A (mtTFA) and mitochondrial DNA polymerase γ (Polg).…”

“…Our findings are consistent with the increased mitochondrial biogenesis that occurs during osteogenic differentiation of mesenchymal stem cells. [35][36][37] This study has limitations. Firstly, the high phosphate was treated for 3 days, and shearing was treated for 1 h. Thus the results mainly reflect the early stage of venous SMC osteogenic transdifferentiation.…”

“…It has been reported that mitochondrial biogenesis increases during the osteogenesis process, for example, osteogenic differentiation of mesenchymal stem cells. [35][36][37] Therefore, we examined the gene expression of mitochondrial transcription factor A (mtTFA) and mitochondrial DNA polymerase γ (Polg). The mitochondrial biogenesis marker mtTFA was up-regulated in the presence of either shear stress alone or high phosphate alone, with an additive effect when combining both treatments (Figure 4A).…”