GSE106586
BMAL1-deficiency contributes to mandibular dysplasia by upregulating MMP3
Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patients. Accordingly, SMH was observed in circadian rhythm-disrupted or BMAL1-deficiency mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1 during the mandibular developmental process. Interestingly, in juvenile SMH patients, we observed that MMP3 level was increased obviously. Consistently, MMP3 was upregulated during the whole growth period of 3 to 10 weeks in Bmal1-/- mice. Given these findings, we set to characterize the underlying mechanism and found that BMAL1-deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together our results provide new insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH Overall design: To gain an independent assessment of the regulatory targets of BMAL1 in Bmal1-/- mBMSCs