A blue-violet laser irradiation stimulates bone nodule formation of mesenchymal stromal cells by the control of the circadian clock protein

Abstract

Mesenchymal stromal cells (MSCs) are multipotent cells, which are present in adult bone marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, and muscle. Their rapid and selective differentiation should provide the potential of new therapeutic approaches for the restoration of damaged or diseased tissue. However, several fundamental questions must be answered before it will be feasible to usefully predict and control MSCs responses to exogenous cytokines or genes. In particular, a better understanding of how specific factor may alter the fate of differentiation of MSCs is needed. In recent reports, circadian clock protein controls osteogenesis in vitro and in vivo. Here we show that a stimulation of a blue-violet laser irradiation regulates the differentiation of mouse MSCs to osteoblasts by change of the localization of a circadian rhythm protein, mouse Cryptochrome 1 (mCRY1). We found that a blue laser irradiation accelerated osteogenesis of MSCs. After laser irradiation, mCRY1 protein was translocated from cytoplasm to nucleus and mCRY1 mRNA level was downregulated thereafter. These results indicate that mCRY1, a blue-violet-light receptor and a master regulator of circadian rhythm, plays important roles in the regulation of the differentiation of MSCs. Since the differentiation of MSCs was easily regulated only by a laser irradiation, the potential of new therapeutic approaches for the restoration of damaged or diseased tissue is anticipated. Furthermore, our results obtained in this study may prove an excellent opportunity to gain insights into cross-talk between circadian rhythms and bone formation.