BMP2 and cancer: For example, Bmal1 controls TGF-β and BMP signaling during brown adipose tissue generation.81 TGF-β is controlled by BMAL1/CLOCK heterodimers, and its circadian rhythm is lost in skeletal muscle tissue with Bmal1 deficiency.82 Also, disruption of Bmal1 in mice promotes cancer metastasis by TGF-β-dependent pathway.83 In MC-3T3 cells and BMSCs overexpressing Bmal1, it was found that Bmal1 upregulates the transcription of Bmp2, thereby upregulating RUNX2 and BMP2 expression, promoting osteogenic differentiation.46,84