CARM1 deficiency inhibits osteoblastic differentiation of bone marrow mesenchymal stem cells and delays osteogenesis in mice |
| |
| Institution: | 1. Department of Medical Cosmetology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;2. Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;3. Department of Plastic Surgery, China-Japan Friendship Hospital, Beijing 100029, China;1. Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China;2. Guizhou Prenatal Diagnosis Center, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China;3. Department of Clinical Biochemistry, School of Medical Laboratory Science, Guizhou Medical University, Guiyang 550004, Guizhou, China;1. Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;2. Center for DNA Repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;3. Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;1. Basic Medical Sciences Center, Shanxi Medical University, Taiyuan, PR China;2. Department of Orthopedics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, PR China;3. Key Laboratory of Cellular Physiology (Shanxi Medical University), Taiyuan, PR China;4. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China;1. Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, China;2. Second Clinical Medical College, Nanchang University, Nanchang 330006, China;3. First Clinical Medical College, Nanchang University, Nanchang 330006, China;4. Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Medical College, Fujian province university, Xiamen 361023, China;5. Department of Burn, The First Affiliated Hospital, Nanchang University, Nanchang 330066, China;1. Department of Plastic Surgery, the first affiliated hospital of Jinan University, No. 613, Huangpu Avenue West, Tianhe District, Guangzhou 510630, China;2. Medical college of Jianghan University, No. 8, Sanjiaohu Road, Wuhan Economic and Technological Development Zone, Wuhan 430014, China;3. Department of Burns and Plastic, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China;4. Innovative Technology Research Institute of Plastic Surgery, Guangzhou 510630, People’s Republic of China;5. Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou 510632, People’s Republic of China |
| |
| Abstract: | Bone repair remains a clinical challenge due to low osteogenic capacity. Coactivator associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that mediates arginine methylation and endochondral ossification. However, the roles of CARM1 in osteoblastic differentiation and bone remodeling have not been explored. In our study, heterozygous CARM1-knockout (KO) mice were generated using the CRISPR-Cas9 system and a model of femoral defect was created. At day 7 postsurgery, CARM1-KO mice exhibited obvious bone loss compared with wild type (WT) mice, as evidenced by reduced bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Deletion of CARM1 in mice lowered synthesis and accumulation of collagen at the injury sites. The alkaline phosphatase (ALP) activity and osteogenic-related gene expression were declined in CARM1-KO mice. To further understand the role of CARM1 in osteoblastic differentiation, bone marrow mesenchymal stem cells (BMSCs) were isolated from the tibia and femur of WT or CARM1-KO mice. CARM1 deletion decreased histone arginine methylation and inhibited osteoblastic differentiation and mineralization. The mRNA sequencing of CARM1-KO BMSCs revealed the possible regulatory molecules by CARM1, which could deepen our understanding of CARM1 regulatory mechanisms. These data could be of interest to basic researchers and provide the direction for future research into bone-related disorders. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
