[A Meta-analysis of alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis].

OBJECTIVE: To assess the efficiency and safety of alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). METHODS: The electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, Chinese BioMedical Literature Database (CBM) and Wanfang Data were searched for all randomized controlled trials (RCT) of alendronate vs. placebo. Two reviewers independently selected trials for inclusion, assessed trial quality using Jadad's scale and extracted the data. RevMan 5.1 software was used for data synthesis and Meta-analysis. RESULTS: Seven studies with 1111 patients were included. Compared with placebo, alendronate significantly increased bone mineral density (BMD) at the lumbar spine[MD = 3.35, 95%CI (2.67-4.02), P = 0.000] and the femoral neck[MD = 1.90, 95%CI (0.89-2.92), P = 0.000] after 12 months of therapy. After 24 months of therapy, alendronate significantly increased BMD at the lumbar spine[MD = 3.91, 95%CI (2.37-5.45), P = 0.000], but not at the femoral neck[MD = 1.91, 95%CI (-1.15-5.02), P = 0.22]. Compared with placebo, no significant reduction was found by the use of alendronate in the incidence of vertebral fractures [RR = 1.00, 95%CI (0.49-2.07), P = 0.99] or nonvertebral fractures [RR = 1.02, 95%CI (0.49-2.14), P = 0.95]. No difference was shown with the adverse event between the two groups[RR = 0.97, 95%CI (0.90-1.05), P = 0.47]. CONCLUSIONS: Alendronate is effective for the prevention and treatment of glucocorticoid-induced bone loss at the lumbar spine and the femoral neck with relatively good safety profile. Yet, there is no significant difference between the two groups in reducing the incidence of vertebral fractures and non-vertebral fractures. Large-scale RCT designed to observe whether different lengths of alendronate therapy will influence the efficiency should be conducted in the future and to further explore whether it can reduce the incidence of fractures.

Knockdown of the HDAC1 promotes the directed differentiation of bone mesenchymal stem cells into cardiomyocytes.

Failure of the directed differentiation of the transplanted stem cells into cardiomyocytes is still a major challenge of cardiac regeneration therapy. Our recent study has demonstrated that the expression of histone deacetylase 1 (HDAC1) is decreased in bone mesenchymal stem cells (BMSCs) during their differentiation into cardiomyocytes. However, the potential roles of HDAC1 in cardiac cell differentiation of BMSCs, as well as the mechanisms involved are still unclear. In current study, the expression of HDAC1 in cultured rat BMSCs is knocked down by lentiviral vectors expressing HDAC1-RNAi. The directed differentiation of BMSCs into cardiomyocytes is evaluated by the expression levels of cardiomyocyte-related genes such as GATA-binding protein 4 (GATA-4), Nirenberg, Kim gene 2 homeobox 5 (Nkx2.5), cardiac troponin T (CTnT), myosin heavy chain (MHC), and connexin-43. Compared with that in control BMSCs, the expression of these cardiomyocyte-related genes is significantly increased in these HDAC1 deficient stem cells. The results suggest that HDAC1 is involved in the cardiomyocyte differentiation of BMSCs. Knockdown of the HDAC1 may promote the directed differentiation of BMSCs into cardiomyocytes.

Downregulation of HDAC1 is involved in the cardiomyocyte differentiation from mesenchymal stem cells in a myocardial microenvironment.

Under myocardial microenvironment, bone marrow-derived mesenchymal stem cells (MSCs) can transdifferentiate into cardiomyocytes (CMs). However, the role of histone deacetylase 1 (HDAC1) in this directed differentiation process remains unclear. The current study is to determine the acetylation regulatory mechanisms that may be involved in the directed CM differentiation from MSCs. MSCs isolated from male Sprague-Dawley (SD) rats were marked with Ad-EGFP and co-cultured with CMs. Flow cytometry was used to sort EGFP-positive (EGFP+) MSCs from the co-culture system. Then, the expression of cardiac troponin T (cTnT) in these MSCs was detected by immunofluorescence assay. In addition, HDAC1 levels at different co-culture times were measured by quantitative real-time polymerase chain reaction (QT-PCR) and Western blotting. At 4 days after co-culture with CMs, the MSCs began to expression detectable levels of cTnT. The expression of HDAC1 in CMs was much lower than that in MSCs. After co-culture with CMs, the expression of HDAC1 in MSCs was significantly decreased in a time dependent manner. In addition, our recent study has also identified that knockdown of the HDAC1 could promote the directed differentiation of MSCs into CMs. The results suggest that HDAC1 has a negative correlation with cardiac cell differentiation from MSCs under a myocardial microenvironment. HDAC1 might play an important role in the directed differentiation of MSCs into CMs in heart.