Chen Ya-Huey, Chung Chiao-Chen, Liu Yu-Chia, Lai Wei-Chen, Lin Zong-Shin, Chen Tsung-Ming, Li Long-Yuan, Hung Mien-Chie
Graduate Institute of Biomedical Sciences, College of Medicine, China Medical UniversityTaichung 40402, Taiwan.
Center for Molecular Medicine, China Medical University HospitalTaichung 40447, Taiwan.
Am J Cancer Res. 2018 Mar 1;8(3):514-525. eCollection 2018.
Mesenchymal stem cells (MSCs) have a high self-renewal potential and can differentiate into various types of cells, including adipocytes, osteoblasts, and chondrocytes. Previously, we reported that the enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, and HDAC9c mediate the osteogenesis and adipogenesis of MSCs. In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine.
间充质干细胞（MSCs）具有很高的自我更新潜力，能够分化为多种类型的细胞，包括脂肪细胞、成骨细胞和软骨细胞。此前，我们报道过，多梳抑制复合物2的催化成分——zeste同源物2（EZH2）增强子和HDAC9c介导间充质干细胞的成骨作用和脂肪生成。在本研究中，我们通过丝裂原活化蛋白激酶（MAPK）抗体阵列筛选确定了p38在成骨分化中的作用，并研究了其转录调控的潜在机制。我们的数据表明，广泛表达的转录因子YY1和HDAC9c协同调节p38的转录活性，以促进其表达，从而增强间充质干细胞的成骨潜能。我们的结果表明，p38介导成骨分化，这对骨相关疾病、骨组织工程和再生医学具有重要意义。
