Henan Joint International Research Laboratory of Stem Cell Medicine, College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, China.
Stem Cell and Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
J Cell Mol Med. 2019 Feb;23(2):1325-1332. doi: 10.1111/jcmm.14034. Epub 2018 Dec 8.
As is previously reported, mesenchymal stem cells have potential ability to differentiate into osteocytes. However, the underlying mechanism during this biological process is poorly understood. In the present study, we identify a novel long non-coding RNA named HOXA-AS2 as a critical regulator during the formation of osteogenesis. Attenuation of HOXA-AS2 can reduce the calcium deposition and repress the alkaline phosphatase activity. Moreover, the expressions of osteogenic marker genes are markedly downregulated after HOXA-AS2 depletion. Mechanistically, we found HOXA-AS2 can regulate the transcriptional activity of NF-κB, a critical inhibitor of osteogenesis. More importantly, HOXA-AS2 knockdown could result in the transcriptional repression of the osteogenic master transcription factor SP7 by a NF-κB/HDAC2-coordinated H3K27 deacetylation mechanism. Based on these studies, we conclude that HOXA-AS2 may serve as a promising therapeutic target for bone tissue repair and regeneration in the near future.
正如之前所报道的，间充质干细胞具有向成骨细胞分化的潜在能力。然而，这一生物学过程的潜在机制仍不清楚。在本研究中，我们鉴定出一种新型长非编码 RNA，命名为 HOXA-AS2，它是成骨形成过程中的一个关键调节因子。HOXA-AS2 的衰减可以减少钙沉积并抑制碱性磷酸酶的活性。此外，HOXA-AS2 耗竭后，成骨标志物基因的表达明显下调。在机制上，我们发现 HOXA-AS2 可以调节 NF-κB 的转录活性，NF-κB 是成骨的关键抑制因子。更重要的是，HOXA-AS2 的敲低可通过 NF-κB/HDAC2 协调的 H3K27 去乙酰化机制导致成骨主转录因子 SP7 的转录抑制。基于这些研究，我们得出结论，HOXA-AS2 可能在不久的将来成为骨组织修复和再生的有前途的治疗靶点。
