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Cell Cycle. 2019 Jul;18(13):1473-1489. doi: 10.1080/15384101.2019.1620572. Epub 2019 May 26.

Deletion of clock gene Bmal1 impaired the chondrocyte function due to disruption of the HIF1α-VEGF signaling pathway.

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a Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education , Medical School of Xi'an Jiaotong University , Xi'an , Shaanxi Province , People's Republic of China.
b Center for Translational Medicine , First Affiliated Hospital of Xi'an Jiaotong University School of Medicine , Xi'an , Shaanxi Province , People's Republic of China.


Several studies have demonstrated the core circadian rhythm gene Bmal1 could regulate the clock control genes (CCGs) expression and maintain the integrity in cartilage tissue. In addition, its abnormal expression is connected with the occurrence and development of several diseases including osteoarthritis (OA). However, the relationship between Bmal1 and cartilage development still needs to be fully elucidated. Here, we bred tamoxifen-induced cartilage-specific knockout mice to learn the effects of Bmal1 on the cartilage development and its underlying mechanisms at specific time points. We observed that Bmal1 ablated mice showed growth retardation during puberty, and the length of whole growth plate and the proliferation zone were both shorter than those in the control group. Deletion of Bmal1 significantly inhibited the chondrocytes proliferation and activated cells apoptosis in the growth plate. Meanwhile, knockout of Bmal1 attenuated the expression of VEGF and HIF1α and enhanced the level of MMP13 and Runx2 in the growth plate chondrocytes. Consistent with these findings in vivo, ablation of Bmal1 could also lead to decrease chondrocytes proliferation, the expression of HIF1α and VEGF and elevate apoptosis in cultured chondrocytes. These findings suggest that Bmal1 plays a pivotal role in cartilage development by regulating the HIF1α-VEGF signaling pathway.


Bmal1; Circadian rhythm; HIF; VEGF; endochondral ossification; growth plate chondrocytes

[Available on 2020-05-26]

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