PMID- 32652777 OWN - NLM STAT- MEDLINE DCOM- 20210322 LR - 20210322 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 34 IP - 9 DP - 2020 Sep TI - Low-magnitude vibration induces osteogenic differentiation of bone marrow mesenchymal stem cells via miR-378a-3p/Grb2 pathway to promote bone formation in a rat model of age-related bone loss. PG - 11754-11771 LID - 10.1096/fj.201902830RRR [doi] AB - The dysfunction of bone marrow mesenchymal stem cells (BMSCs) in osteogenic differentiation is one of the main causes of age-related bone loss. Our previous studies have shown that low-magnitude vibration (LMV) induces the osteogenic differentiation of BMSCs derived from ovariectomized osteoporotic rats. To investigate whether LMV promotes osteogenic differentiation of BMSCs and its underlying mechanisms in aged rats, 20-month-old female Sprague-Dawley rats (n = 20) were randomly divided into LMV group (rats were vibrated at 0.3 g and 90 Hz for 30 minutes, once daily, 5 days a week until 12 weeks for subsequent analysis, n = 10), static group (rats were placed in the box on the vibration platform without vibration, n = 10); 6-month-old female Sprague-Dawley rats were used as control (young group, n = 10). The bone mineral density and bone strength of aged rats were significantly decreased compared with the young rats. Furthermore, the primary BMSCs isolated and cultured from the aged rats with the whole-bone marrow differential pasting method showed a decreased ability in osteogenic differentiation compared with that from the young rats. Then the differentially expressed miRNAs between the aged and young rat-derived BMSCs were screened by high-throughput sequencing and verified by qRT-PCR, and we found that miR-378a-3p was significantly downregulated in the aged rat-derived BMSCs compared with the young rat-derived BMSCs. By transfecting miRNA mimics and inhibitors, miR-378a-3p was confirmed to promote the expression levels of osteogenic genes (Runx2, ALP, Col I, and OCN) and ALP activity of the aged rat-derived BMSCs. Meanwhile, the expression levels of osteogenic genes and miR-378a-3p of aged rat-derived BMSCs were significantly upregulated by LMV (cells were vibrated at 0.3 g and 90 Hz for 30 minutes a day, until 5 days for subsequent analysis), while the LMV-induced osteogenic gene expression levels of aged rat-derived BMSCs were suppressed by miR-378a-3p inhibitors. Furthermore, the inhibition of growth factor receptor-bound protein 2 (Grb2) by miR-378a-3p and Grb2-siRNA promoted the LMV-induced osteogenic differentiation of aged rat-derived BMSCs. Additionally, LMV was found to promote bone mineral density and bone strength of aged rats in vivo, as well as upregulating the expression level of miR-378a-3p and downregulating the expression level of Grb2 of BMSCs from aged rats. These results suggest that LMV induces osteogenic differentiation of BMSCs through miR-378a-3p/Grb2 pathway to improve bone mineral density and mechanical properties in a rat model of age-related bone loss. CI - (c) 2020 Federation of American Societies for Experimental Biology. FAU - Yu, Xiaoqin AU - Yu X AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. FAU - Zeng, Ye AU - Zeng Y AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. FAU - Bao, Mingyue AU - Bao M AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. FAU - Wen, Jirui AU - Wen J AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. FAU - Zhu, Guangguang AU - Zhu G AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. FAU - Cao, Chengjian AU - Cao C AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. FAU - He, Xueling AU - He X AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. AD - Laboratory Animal Center, Sichuan University, Chengdu, China. FAU - Li, Liang AU - Li L AD - Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200711 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (GRB2 Adaptor Protein) RN - 0 (Grb2 protein, rat) RN - 0 (MIRN378 microRNA, rat) RN - 0 (MicroRNAs) SB - IM MH - Age Factors MH - Animals MH - Bone Density/genetics MH - Bone Marrow Cells/cytology/*metabolism MH - Cell Differentiation/*genetics MH - Cells, Cultured MH - Disease Models, Animal MH - Female MH - GRB2 Adaptor Protein/*genetics/metabolism MH - Gene Expression Profiling/methods MH - Gene Expression Regulation MH - Mesenchymal Stem Cells/cytology/*metabolism MH - MicroRNAs/*genetics MH - Osteogenesis/*genetics MH - Osteoporosis/*genetics/metabolism MH - Rats, Sprague-Dawley MH - *Vibration OTO - NOTNLM OT - age-related bone loss OT - bone marrow mesenchymal stem cells OT - growth factor receptor-bound protein 2 OT - low-magnitude vibration OT - miR-378a-3p OT - osteogenic differentiation EDAT- 2020/07/12 06:00 MHDA- 2021/03/23 06:00 CRDT- 2020/07/12 06:00 PHST- 2019/11/10 00:00 [received] PHST- 2020/06/15 00:00 [revised] PHST- 2020/06/19 00:00 [accepted] PHST- 2020/07/12 06:00 [pubmed] PHST- 2021/03/23 06:00 [medline] PHST- 2020/07/12 06:00 [entrez] AID - 10.1096/fj.201902830RRR [doi] PST - ppublish SO - FASEB J. 2020 Sep;34(9):11754-11771. doi: 10.1096/fj.201902830RRR. Epub 2020 Jul 11.