Guozheng Zhu1,2, Canjun Zeng3,4,5,6, Yuepeng Qian3,4,5,6, Song Yuan7, Zelin Ye1,2, Shanwen Zhao3,4,5,6, Runguang Li3,4,5,6,8. 1. Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China. 2. Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. 3. Department of Foot and Ankle Surgery, Center for Orthopaedic Surgery, the Third Affiliated Hospital of Southern Medical University, Guangzhou, China. 4. Orthopaedic Hospital of Guangdong Province, Guangzhou, China. 5. Academy of Orthopaedics, Guangdong Province, Guangzhou, China. 6. Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, Guangzhou, China. 7. Department of Orthopedics, Linzhi people's hospital, Linzhi, China. 8. Department of Orthopedics, Linzhi people's hospital, Linzhi, China. lirunguang79@163.com.
Abstract
BACKGROUND: With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. METHODS: A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. RESULTS: We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNA-MEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. CONCLUSION: Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosis.
BACKGROUND: With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. METHODS: A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. RESULTS: We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNA-MEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. CONCLUSION: Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosis.
Authors: John T Connelly; Eric J Vanderploeg; Janna K Mouw; Christopher G Wilson; Marc E Levenston Journal: Tissue Eng Part A Date: 2010-06 Impact factor: 3.845
Authors: Shelley E Keating; Daniel A Hackett; Helen M Parker; Helen T O'Connor; James A Gerofi; Amanda Sainsbury; Michael K Baker; Vivienne H Chuter; Ian D Caterson; Jacob George; Nathan A Johnson Journal: J Hepatol Date: 2015-04-08 Impact factor: 25.083