Recent advances in deep sequencing technologies have revealed that, while less than 2% of the human genome is transcribed into mRNA for protein synthesis, over 80% of the genome is transcribed, leading to the production of large amounts of noncoding RNAs (ncRNAs). It has been shown that ncRNAs, especially long non-coding RNAs (lncRNAs), may play crucial regulatory roles in gene expression. As one of the first isolated and reported lncRNAs, H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Mechanistically, H19 mediates diverse regulatory functions by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, modular scaffold, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Here, we summarized the current understanding of H19 in embryogenesis and development, cancer development and progression, mesenchymal stem cell lineage-specific differentiation, and metabolic diseases. We discussed the potential regulatory mechanisms underlying H19's functions in those processes although more in-depth studies are warranted to delineate the exact molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. Ultimately, these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

BMP9 mediated osteogenic differentiation mechanisms of MSCs were widely explored, however, mechanisms of BMP9-induced angiogenesis still need to be clarified. We previously characterized that Notch1 promoted BMP9-induced osteogenesis–angiogenesis coupling process in mesenchymal stem cells (MSCs). Here, we explored the underlying mechanisms of lncRNA H19 (H19) mediated regulation of BMP9-induced angiogenesis through activating Notch1 signaling. We demonstrated that basal expression level of H19 was high in MSCs, and silencing H19 attenuates BMP9-induced osteogenesis and angiogenesis of MSCs both in vitro and in vivo. Meanwhile, we identified that BMP9-induced production of CD31⁺ cells was indispensable for BMP9-induced bone formation, and silencing H19 dramatically blocked BMP9-induced production of CD31⁺ cells. In addition, we found that down-regulation of H19 inhibited BMP9 mediated blood vessel formation and followed subsequent bone formation in vivo. Mechanistically, we clarified that H19 promoted p53 phosphorylation by direct interacting and phosphorylating binding, and phosphorylated p53 potentiated Notch1 expression and activation of Notch1 targeting genes by binding on the promoter area of Notch1 gene. These findings suggested that H19 regulated BMP9-induced angiogenesis of MSCs by promoting the p53-Notch1 angiogenic signaling axis.

Bleeding patients exhibit different fibrinolytic phenotypes after injury, and the universal use of tranexamic acid (TXA) is doubted. We aimed to evaluate the efficacy of postoperative antifibrinolytic treatment in total hip arthroplasty (THA) patients with different fibrinolytic phenotypes. A retrospective analysis was conducted in 238 patients who underwent THA. Patients were divided into two groups by different fibrinolytic phenotypes (non-fibrinolytic shutdown and fibrinolytic shutdown), determined by the LY30 level on postoperative day 1 (POD1). The two groups were further stratified into four sub-groups based on different postoperative TXA regimens (Group A received no TXA postoperatively, while Group B did). Hidden blood loss (HBL), decline of hemoglobin (ΔHb), D-dimer (D-D), fibrinogen/fibrin degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), and demographics were collected and compared. The clinical baseline data were comparable between the studied groups. In patients who presented non-fibrinolytic shutdown postoperatively, Group B suffered significantly lower HBL and ΔHb than Group A on POD3 and POD5. In patients who presented postoperative fibrinolytic shutdown, Group B failed to benefit from the postoperative administration of TXA when compared to Group A. No difference was found in postoperative levels of D-D, FDP, PT, and APTT. Postoperative antifibrinolytic therapy is beneficial for THA patients who presented non-fibrinolytic shutdown postoperatively, while the efficacy and necessity should be considered with caution in those with fibrinolytic shutdown. LY30 is a promising parameter to distinguish different fibrinolytic phenotypes and guide TXA administration. However, further prospective studies are needed to confirm these findings.