The role of mitochondria in osteogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering due to their differentiation potential along various cell types. In recent years, accumulating evidence has suggested that the regulation of mitochondria dynamics and function is essential for successful differentiation of MSCs. In this paper, we review and provide an integrated view on the role of mitochondria in MSC differentiation. The mitochondria are maintained at a relatively low activity level in MSCs, and upon induction, mtDNA copy number, protein levels of respiratory enzymes, the oxygen consumption rate, mRNA levels of mitochondrial biogenesis-associated genes, and intracellular ATP content are increased. The regulated level of mitochondrial ROS is found not only to influence differentiation but also to contribute to the direction determination of differentiation. Understanding the roles of mitochondrial dynamics during MSC differentiation will facilitate the optimization of differentiation protocols by adjusting biochemical properties, such as energy production or the redox status of stem cells, and ultimately, benefit the development of new pharmacologic strategies in regenerative medicine.

Keywords: differentiation; mesenchymal stem cells; mitochondria.

Figure 1

The regulation of mitochondria dynamics and function is essential for successful differentiation of MSCs. Mitochondria are mainly seen gathered around the nucleus in MSCs, whereas the mitochondria are more uniformly distributed in the cytoplasm of differentiated cells. Along with the process of differentiation, the morphology of mitochondria gradually becomes slender, and the number of mitochondria increases. The metabolic pattern has changed from glycolysis to oxidative phosphorylation; therefore, increased oxygen consumption and respiratory enzyme complex activation becomes logical. Notably, the membrane potential appears to be reduced in differentiated cells. The advancement of age and the high level of ROS can promote MSCs to adipocytes, whereas a low level of ROS can promote osteogenesis