BACKGROUND DATA AND OBJECTIVE: Mesenchymal stem cells (MSCs) are multipotent 
cells present in adult bone marrow that replicate as undifferentiated cells and 
can differentiate to lineages of mesenchymal tissues. Homeostatic control of 
bone remodeling maintains bone mass by ensuring that bone resorption and bone 
formation occur sequentially and in a balanced manner. As most homeostatic 
functions occur in a circadian manner, a circadian clock could control bone 
mass. Here we show that laser irradiation can direct the extracellular 
calcification of mouse MSCs by altering the intracellular localization of the 
circadian rhythm protein cryptochrome 1 (CRY1).
MATERIALS AND METHODS: MSCs were irradiated with a blue laser (wavelength 405 
nm) for 180 sec via a fiber attached to the bottom of the culture dish. After 
laser irradiation, the MSCs were incubated in osteogenic differentiation medium 
for 5 d. After laser irradiation, circadian rhythm protein CRY1 was 
immunostained and histochemical staining for extracellular calcification was 
observed.
RESULTS: Laser irradiation promoted extracellular calcification of MSCs, induced 
the translocation of CRY1 protein from the cytoplasm to the nucleus, and 
decreased CRY1 mRNA levels quantified by real-time PCR. Since the timing of 
nuclear accumulation of clock proteins constitutes an important step in the 
transcription-translation feedback loop driving the circadian core oscillator, 
laser irradiation could provide a simple and effective technology for clock 
protein localization and turnover. Our results also indicate that CRY1 is a 
master regulator of circadian rhythm that regulates the extracellular 
calcification of MSCs.
CONCLUSION: Laser irradiation could provide a simple and effective means of 
controlling the fate of MSCs as a therapeutic strategy, and act as a "molecular 
switch" of regulatory proteins by suppressing CRY transcription. Furthermore, 
this model system may be useful for exploring the cross-talk between circadian 
rhythm and cell function.