BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3

Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Jiajia Zhao, Xin Zhou, Qingming Tang, Ran Yu, Shaoling Yu, Yanlin Long, Cen Cao, Jun Han, Anbing Shi, Jeremy J. Mao, Xiong Chen, Lili Chen 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-deficient mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1. Interestingly, in juvenile SMH patients, we observed that MMP3 was obviously increased. Consistently, MMP3 was upregulated during the whole growth period of 3–10 weeks in Bmal1 −/− mice. Given these findings, we set out to characterize the underlying mechanism and found BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together, our results provide insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH. Teaser Chen et al. found that BMAL1 expression decreased significantly in the mandibles of juvenile SMH patients, and SMH was observed in circadian-rhythm-disrupted mi...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research