DLX3 promotes bone marrow mesenchymal stem cells proliferation through H19/miR-675 axis

The underlying molecular mechanism of the increased bone mass phenotype in Tricho-dento-osseous (TDO) syndrome remains largely unknown. Our previous study has shown that the TDO point mutation c.533A>G, Q178R in DLX3 could increase bone density in a TDO patient and transgenic mice partially through delaying senescence in bone marrow mesenchymal stem cells (BMSCs). In the present study, we provided a new complementary explanation for TDO syndrome: the DLX3 (Q178R) mutation increased BMSCs proliferation through H19/miR-675 axis. We found that BMSCs derived from the TDO patient (TDO-BMSCs) had stronger proliferation ability than controls by clonogenic and CCK-8 assays. Next, experiments of overexpression and knockdown of wild type DLX3 via lentiviruses in normal BMSCs confirmed the results by showing its negative role in cells proliferation. Through validated high-throughput data, we found that the DLX3 mutation reduced the expression of H19 and its co-expression product miR-675 in BMSCs. Function and rescue assays suggested that DLX3 , long non-coding RNA H19 and miR-675 are negative factors in modulation of BMSCs proliferation as well as NOMO1 expression. The original higher proliferation rate and the expression of NOMO1 in TDO-BMSCs were suppressed after H19 restoration. Collectively, it indicates that DLX3 regulates BMSCs proliferation through H19/miR-675 axis. Moreover, the increased expression of NOMO1 and decreased H19/miR-675 expression in DLX3 (Q178R) transg...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research