Abstract
BackgroundControlling cellular functions, including stem cell growth and differentiation, can be the key for the treatment of metabolic disorders, such as type II diabetes mellitus (T2DM). Previously identified as peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, betulinic acid (BA) may have the capability to control stem cell homeostasis, benefiting T2DM treatment. In this study, the effects of BA on osteogenesis and adipogenesis mechanisms of human mesenchymal stem cells (hMSCs) were investigated.ResultsWe observed that BA increased hMSC osteogenesis by enhancing the alkaline phosphatase activity, calcium deposition, and mRNA expressions of osteogenic markers, namely, runt-related transcription factor 2, osteocalcin, and osteopontin. In addition, BA decreased hMSC adipogenesis with the decrease in glycerol-3-phosphate dehydrogenase activity, reduced intracellular lipid accumulations, down-regulated CCAAT-enhancer-binding protein alpha, and suppressed post-transcriptional adiponectin and leptin secretion. BA increased the brown adipocyte characteristics with the increase in the ratio of small lipid droplets and glucose uptake. Furthermore, the mRNA expressions of brown adipocyte markers, namely, PPARγ coactivator one alpha, uncoupling protein 1, and interleukin-6 increased.ConclusionsOur results uncovered the mechanisms of how BA improved glucose and lipid metabolisms by decreasing white adipogenesis and increasing brown adipogenesis. Altogether, BA may be used for balancing glucose metabolisms without the potential side effects on bone loss or weight gain.
Highlights
Human mesenchymal stem cells are progenitor cells of mesenchymal lineage tissues, including muscle, cartilage, bone, and fat
betulinic acid (BA) increased the metabolic activity of human mesenchymal stem cells (hMSCs) during adipogenesis To track the changes in the metabolic activity of hMSCs in response to BA, we performed alamarBlue assays on days 7 and 10, proliferating phase, osteogenic differentiation, or adipogenic differentiation
The results showed that BA caused no alteration in the metabolic activity of hMSCs during the proliferating phase or osteogenic differentiation
Summary
Human mesenchymal stem cells (hMSCs) are progenitor cells of mesenchymal lineage tissues, including muscle, cartilage, bone, and fat. Within these tissues, several of the hMSCs are left as undifferentiated adult stem cells. The overexpansion of adipose tissue in obesity has an inverse effect on bone metabolisms by decreasing bone formation through the competitive utilization of the same mesenchymal progenitor cells and increasing bone resorption by inducing osteoclast activation with pro-inflammatory cytokine secretion (Abdallah, 2017; Cao, 2011; James, 2013; Lacey et al, 2009; Sonowal et al, 2013). Controlling cellular functions, including stem cell growth and differentiation, can be the key for the treatment of metabolic disorders, such as type II diabetes mellitus (T2DM). The effects of BA on osteogenesis and adipogenesis mechanisms of human mesenchymal stem cells (hMSCs) were investigated. BA may be used for balancing glucose metabolisms without the potential side effects on bone loss or weight gain
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