Bmal1 induces osteoblast differentiation via regulation of BMP2 expression in MC3T3-E1 cells

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• 作者：Hyeon-Young Min^a ; ^b ; ^{jminhy@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Kyeong-Min Kim^a ; ^b ; ^{kkm97655@naver.com" class="auth_mail" title="E-mail the corresponding author} ; Gabbine Wee^c ; ^{gabbine@dgmif.re.kr" class="auth_mail" title="E-mail the corresponding author} ; Eun-Jung Kim^b ; ^{ejkim4164@gamil.com" class="auth_mail" title="E-mail the corresponding author} ; Won-Gu Jang^a ; ^b ; ^{jangwg@daegu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bmal1 ; brain and muscle Arnt-like 1 ; BMP2 ; bone morphogenetic protein-2 ; Id1 ; inhibitor of DNA binding ; KO ; knockout ; OC ; osteocalcin ; Runx2 ; Runt-related transcription factor 2
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：162
• 期：Complete
• 页码：41-46
• 全文大小：466 K

文摘

Mammalian circadian rhythms regulate many metabolic processes. Recent studies suggest that brain and muscle Arnt-like 1 (BMAL1), an important component of mammalian circadian rhythm, is associated with insulin signaling. Several studies have shown that insulin is associated with bone metabolism; however, the relationship between BMAL1 and osteoblasts remains unclear.

<h4 id="absSec_2">Main methodsh4>

Expression of osteogenic markers and Bmal1 in MC3T3-E1 cells was measured by RT-PCR and Western blotting. Alizarin red S staining was performed to assess matrix mineralization in MC3T3-E1 cells.

<h4 id="absSec_3">Key findingsh4>

mRNA levels of osteogenic genes and Bmal1 were up-regulated in MC3T3-E1 cells upon insulin treatment. In addition, Bmal1 overexpression increased the expression of osteogenic genes including inhibitor of DNA binding (Id1), Runt-related transcription factor 2 (Runx2), and osteocalcin (OC). Interestingly, expression of Bone morphogenetic protein-2 (BMP2), an important upstream factor of Id1, Runx2, and OC, was markedly increased by Bmal1. Finally, we confirmed that insulin-induced BMP2 expression was attenuated in Bmal1 knockout (KO) cells. PCR analysis and alizarin red S staining showed that insulin-mediated increases gene expression and calcium deposition were reduced in Bmal1 KO cells compared to wild-type cells.

<h4 id="absSec_4">Significanceh4>

Taken together, these results demonstrate that Bmal1 promotes osteoblast differentiation by regulating BMP2 expression in MC3T3-E1 cells.