Cartilage injury is difficult to repair since the cartilage tissue lacks self-restoration ability. Improved formation of chondrocytes differentiated from the mesenchymal stem cells (MSC) by genetic regulation is a potentially promising therapeutic option. SOX9 is a critical transcription factor for mesenchymal condensation prior to chondrogenesis. Previous studies demonstrated that several microRNAs (miRNAs or miRs) play a critical role in the chondrogenic differentiation of MSCs. However, the interactional relations between miR-30a and SOX9 during chondrogenic differentiation of MSCs need to be further elucidated. In the present study, human bone marrow-derived mesenchymal stem cells have been isolated and induced into chondrogenic differentiation to imitate the cartilage formation in vitro. Additionally, the expression levels of several miRNAs that were reported to interact with the SOX9 3′untranslated region (UTR) were examined by using reverse transcription-quantitative PCR. The interactional relations between candidate miRNAs and SOX9 were verified with the transfection of a miRNA mimic or inhibitor and a luciferase reporter gene assay. The results indicate that miR-30a and miR-195 were consistently increased during MSC chondrogenic differentiation. Additionally, the binding of miR-30a to the SOX9 3UTR was verified. Then, the authors upregulated the expression of miR-30a and found that MSC chondrogenic differentiation was inhibited. Taken together, the results of the present study demonstrate that miR-30a has a negative regulatory effect on MSC chondrogenic differentiation by targeting SOX9. Advances in epigenetic regulating methods will likely be the future of systemic treatment of cartilage injury.

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Background Osteopenia have been well documented in adolescent idiopathic scoliosis (AIS). Adiponectin has been shown to be inversely proportional to body mass index and to affect bone metabolism. However, the circulating levels of adiponectin and the relationship between adiponectin and low bone mass in AIS remain unclear. Methods A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA) in the AIS and control groups. An improved multiplex ligation detection reaction was performed to study on single nucleotide polymorphism. Facet joints were collected and used to measure the microstructure, the expression of RANKL, OPG, osteoblast-related genes, inflammatory factors, adiponectin and its receptors by qPCR, western blotting and immunohistochemistry. Furthermore, primary cells were extracted from facet joints to observe the reaction after adiponectin stimulation. Results Compared with the controls, lower body mass index and a marked increase in circulating adiponectin were observed in AIS osteopenia (17.09 ± 1.09 kg/m 2 and 21.63 ± 10.30 mg/L). A significant difference in the presence of rs7639352
was detected in the AIS osteopenia, AIS normal bone mass and control groups. The T allele showed a significant higher proportion in AIS osteopenia than AIS normal bone mass and control groups (41.75% vs 31.3% vs 25.7%, p < 0.05). micro-CT demonstrated that the AIS convex side had a significant lower bone volume than concave side. RNA and protein analyses showed that in cancellous bone, higher RANKL/OPG and adipoR1 levels and lower runx2 levels were observed, and in cartilage, higher adipoR1 and IL6 levels were observed in AIS. Furthermore, convex side had higher RANKL/OPG, IL6 and adipoR1 than concave side. Compared with normal primary cells, convex side primary cells showed the most acute action, and concave side primary cells showed the second-most acute action when exposed under same adiponectin concentration gradient. Conclusion Our results indicated that high circulating adiponectin levels may result from gene variations in AIS osteopenia. Adiponectin has a negative effect on bone metabolism, and this negative effect might be mediated by the ADR1-RANKL/OPG and ADR1-IL6 pathways. Electronic supplementary material The online version of this article (10.1186/s12967-019-1805-7) contains supplementary material, which is available to authorized users.

Idiopathic scoliosis (IS) is a disease with unknown etiology characterized by spinal rotation asymmetry. Reports describing the histochemical and pathological analyses of IS patients have shown that necrosis, fibrosis and fatty involution occurred on the apex paraspinal muscles. However, research on the changes in the paraspinal muscles of IS patients compared with those in matched controls is rare; thus, the basic mechanism of how paraspinal muscles are injured in IS patients is still unclear. In this study, we investigated the morphological changes of paraspinal muscles in the control group and IS patients, and the possible mechanisms were examined in vivo and in vitro. Increased myofiber necrosis was found on both sides of the apex paraspinal muscles of IS patients compared with those of the control group, and the number of TUNEL-positive apoptotic cells was also increased. Apoptosis signaling pathways, including pro-apoptosis proteins such as cleaved-caspase 3 and cytochrome c, were markedly upregulated, whereas the anti-apoptotic Bcl-2/Bax was significantly downregulated in IS patients compared with the control group. Moreover, PGC-1α and SOD1 were upregulated in accordance with the increased ROS production in IS patients. The distribution of myofiber types, as well as the mRNA levels of type IIa myofiber marker MYH2 and the important myogenesis regulator MYOG were remarkably changed in IS patients. In addition, C2C12 or human skeletal muscle mesenchymal progenitor cells treated with antimycin A in glucose-free and serum-free culture medium, which can activate oxidative stress and induce apoptosis, showed similar patterns of the changed distribution of myofiber types and downregulation of MYH2 and MYOG. Altogether, our study suggested that the extents of severe muscle injury and accumulated oxidative stress were increased in IS patients compared with the control group, and the abnormal myogenesis was also observed in IS patients. Since elevated oxidative stress can lead to apoptosis and the dysregulation of myogenesis in muscle cells, it may be associated with the pathological changes observed in IS patients and contribute to the development and progression of IS.