Mir-21 regulates osteogenesis and chondrogenesis of mesenchymal stem cells

Liangliang Xu, Yuxin Sun, Gang Li
2016 Journal of Orthopaedic Translation  
MicroRNAs are noncoding, small RNAs, 21e25nt in length, encoded in the genome, which can regulate the gene expression by targeting the 3' untranslated region (UTR) of mRNAs at the post-transcriptional level. Emerging evidences suggest that microRNAs play important roles in osteogenesis and skeletal homeostasis. Recent studies indicated the significant regulatory function of mir-21 in osteogenesis in vitro, but the effect of mir-21 on multi-lineage differentiation ability of mesenchymal stem
more » ... esenchymal stem cells is not fully revealed. In the present study, we aimed to investigate the effect of mir-21 intervention on osteogenic and chondrogenic differentiation of rat bone marrow derived MSCs in vitro and in vivo. Results: The results showed that the up-regulation of mir-21 promoted osteogenesis and chondrogenesis of MSCs. Not only did mir-21 increase the expression of osteopontin and alkaline phosphatase in rBMSCs, but also promote mineralisation in the condition of osteogenic induction. Furthermore, using the open femur fracture model, we found that the bone healing properties were also improved by mir-21 overexpressing MSCs according to the results of microCT, mechanical test, and histological analysis. Discussion and Conclusion: In conclusion, this study demonstrated that the over expression of mir-21 could promote osteogenesis and chondrogenesis. In addition, mir-21 overexpressing MSCs could accelerate bone fracture healing, which may contribute to a new therapeutic way for fracture repair. http://dx.Distraction osteogenesis (DO) could successfully induce large-size bone defect regeneration, but DO usually requires a long duration of bone consolidation. Developing innovative approaches to augment bone consolidation during DO is in burning need. Staphylococcal enterotoxin C2 (SEC2) has been developed and found to suppress osteoclastogenesis of mesenchymal stem cells in vitro. In this study, we investigated the effect of SEC2 on the proliferation of rat bone marrow derived mesenchymal stem cells (rBMSCs) and osteogenic differentiation of rBMSCs. Furthermore, we locally administrated SEC2 (10ng/ml) or PBS into the gap in a rat DO model every three days until termination. The distraction regenerates were subjected to X-rays, micro-computed tomography (mCT), and mechanical testing. Histology and immunohistochemistry examinations were used to assess new bone quality. For the results, SEC2 had no effect on cell viability. The calcium deposition was remarkably increased and the osteogenic markers were significantly up-regulated in the rBMSCs treated with SEC2. In the animal model, the SEC2 group had higher bone volume/total tissue volume in the regenerates. Greater force was required to break the SEC2-treated tibiae in four-point testing. Improvement of new bone properties were also confirmed by histological analysis. Osteocalcin and osterix expression were up-regulated in the SEC2 group. This study demonstrated that SEC2 local injection promoted osteogenesis and enhanced bone consolidation during DO. The findings support the application of SEC2 as a potential novel strategy to expedite bone consolidation in patients undergoing DO treatment. http://dx.Introduction: Rotator cuff (RC) tendons are often prone to lesions, as 30e50% of the population over 50 years of age suffer from partial-and full-thickness RC tears. A torn rotator cuff is a disruption in the integrity of the tendon at the insertion into the humeral head. Damaged RC heals very slowly and rarely attains the structural integrity and mechanical strength of normal, undamaged RC. It has been reported that addition of BMSCs to the injured RC insertion site did not improve the outcome [1]. Interestingly, the same authors found that BMSCs overexpressed with scleraxis significantly improve RC healing [2]. Tendon derived stem cells, with highly expressed scleraxis [3,4], may be an alternative cell
doi:10.1016/j.jot.2016.06.103 fatcat:i5gpe4wrgvattjojk2adt6ux2i