Bre Enhances Osteoblastic Differentiation by Promoting the Mdm2-Mediated Degradation of p53

Abstract

Bre is a conserved cellular protein expressed in various tissues. Its major function includes DNA damage repair and anti-apoptosis. Recent studies indicate that Bre is potentially involved in stem cell differentiation although pathophysiological significance along with the molecular mechanisms is still unclear. Here, we report that Bre protein was substantially expressed in the bone tissue and its expression was highly upregulated during the osteogenic differentiation. To test a hypothesis that Bre plays functional roles in the process of osteogenic differentiation, we examined the expression of Bre in an osteoporosis mouse model. Compared with the normal bone tissue, Bre expression in osteoporotic bone was also significantly reduced. Moreover, knockdown of Bre in the mouse bone marrow mesenchymal cells significantly reduced the expression of osteogenic marker genes, the alkaline phosphatase activity, and the mineralization capacity, while overexpression of Bre greatly promoted the osteogenesis both in vitro and in vivo. Interestingly, we founded that knockdown of Bre led to activation of the p53 signaling pathways exhibited by increased p53, p21, and Mdm2. However, when we inhibited the p53 by siRNA silencing or pifithrin-α, the impaired osteogenesis caused by Bre knockdown was greatly restored. Finally, we found that Bre promoted the Mdm2-mediated p53 ubiquitination and degradation by physically interacting with p53. Taken together, our results revealed a novel function of Bre in osteoblast differentiation through modulating the stability of p53. Stem Cells 2017;35:1760-1772.

STAT1, IGF1, RAC1, and MDM2 Are Associated with Recurrence of Giant Cell Tumor of Bone

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MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by targeting MDM2

“…Anesthesia-induced cognitive impairment is considered to be the most common type of postoperative cognitive impairment. Previous studies have demonstrated that extended exposure to anesthetics resulted in excessive apoptosis of neurons and decreased the self-renewal capacity of neural stem cells, which consequently led to learning and memory deficits in animals ( 37 – 41 ). miRNA dysregulation has been previously associated with neurodegeneration induced by anesthesia ( 6 , 15 , 24 ).…”

Single-cell RNA-sequencing analysis identifies host long noncoding RNA MAMDC2-AS1 as a co-factor for HSV-1 nuclear transport

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