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The nuclear receptor corepressor (N-CoR) is involved in the regulation of diverse transcription factors. We previously found that N-CoR could regulate adipogenic differentiation of rat mesenchymal stem cells (MSCs), but whether it modulated osteogenic differentiation of this type of cells was uncertain. Therefore, in the present study, we investigated the effect and mechanism of N-CoR on osteogenic differentiation of rat MSCs. The results showed that MSCs cultured in osteogenic medium successfully differentiated into osteogenic cells. Overexpression of N-CoR decreased cell proliferation, alkaline phosphatase (ALP) activity, calcium accumulation, mRNA expression of genes including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), Osterix and Runx2, and protein expression of phosphor-Akt (pAkt). Conversely, knocking down cellular N-CoR by small interfering RNA (siRNA) promoted pAkt activity and cell differentiation. Overexpression or knockdown of N-CoR had no significant influences on the protein expression of pyruvate dehydrogenase kinase isozyme 1 (PDK1), phosphatidylinositol 3-kinase (PI3K) and total Akt, indicating that N-CoR regulated the changes in the PI3K/Akt signaling pathway by targeting pAkt. To further prove the function of the PI3K/Akt signaling in N-CoRregulated osteogenic differentiation, we used the PI3K inhibitor (LY294002) to block the activation of the PI3K/Akt pathway and found that overexpression of N-CoR showed no effects on ALP activity, calcium level and mRNA expression of BSP, osteocalcin OCN, OPN, Osterix and Runx2 in rat MSCs following the inhibition of the PI3K/Akt pathway. These findings suggest that N-CoR regulates osteogenic differentiation of rat MSCs through suppression of the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) have been confirmed to induce bone quality deterioration in diabetes mellitus (DM), and to associate with abnormal expression of miRNAs in DM patients or in vitro. Recently, miRNAs have been recognized to mediate the onset or progression of DM. In the present study, we investigated the regulation on miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells, with real-time quantitative PCR assay. And then we examined the inhibition of insulin-like growth factor 1 receptor (IGF-1R) expression by miR-223, via targeting of the 3′ UTR of IGF-1R with real-time quantitative PCR, western blotting and luciferase reporter assay. Then we explored the regulation of miR-223 and IGF-1R levels, via the lentivirus-mediated miR-223 inhibition and IGF-1R overexpression in the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It was demonstrated that AGE-BSA treatment with more than 100 μg/ml significantly up-regulated miR-223 level, whereas down-regulated IGF-1R level in MC3T3-E1 cells. And the up-regulated miR-223 down-regulated IGF-1R expression in both mRNA and protein levels, via targeting the 3′ UTR of IGF-1R. Moreover, though the AGE-BSA treatment promoted apoptosis in MC3T3-E1 cells, the IGF-1R overexpression or the miR-223 inhibition significantly attenuated the AGE-BSA-promoted apoptosis in MC3T3-E1 cells. In summary, our study recognized the promotion of miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells. The promoted miR-223 targeted IGF-1R and mediated the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It implies that miR-223 might be an effective therapeutic target to antagonize the AGE-induced damage to osteoblasts in DM. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare Smith-Petersen osteotomy (SPO), poly-segmental wedge osteotomy (PWO) and pedicular subtraction osteotomy (PSO) in patients with rigid thoracolumbar kyphosis primarily caused by ankylosing spondylitis. The efficiency, efficacy and safety of these three osteotomies have not been compared systematically, and no illness-oriented surgical type selection strategy for the treatment of ankylosing spondylitis related to non-angular kyphosis has been reported.Methods: The inclusion and exclusion criteria were defined, and 19 electronic databases were searched for eligible studies without language limitations. For the included studies, data extraction, bias analysis, heterogeneity analysis and quantitative analysis were performed to analyze the correction of kyphosiskyphosis and the incidence of complications.Results: Nine comparative studies that met the standards were included with a total of 539 patients that underwent SPO (n = 120), PWO (n = 119), or PSO (n = 300). The correction of kyphosis by PSO was 8.74° [95% CI: 0.7-16.78] greater than SPO. The correction of kyphosis by PWO was 13.88° [95 % CI: 9.25-18.51] greater than SPO. For local biomechanical complications, the pooled risk ratio of PWO to PSO was 1.97 [95 % CI: 1.03-3.77]. For blood loss, PSO was 806.42 ml [95% CI: 591.72-1021.12] greater than SPO and 566.76 ml [95 % CI: 129.80-1003.72] greater than PWO.Conclusions: To treat rigid thoracolumbar kyphosis, PSO showed higher efficiency and efficacy than SPO, and PWO had a higher efficacy than SPO. The risk of local biomechanical complications was greater in PWO than PSO. Bleeding was more severe in PSO than in SPO or PWO. The incidence of neural complications and systemic complications was similar. [ABSTRACT FROM AUTHOR]