Jiali Tan

Decreased osteogenesis of adult mesenchymal stem cells by reactive oxygen species under cyclic stretch: a possible mechanism of age related osteoporosis

Age related defect of the osteogenic differentiation of mesenchymal stem cells (MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation. Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats. Accordingly, there were much more reactive oxygen species (ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1 (SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.

Dual loading miR-218 mimics and Temozolomide using AuCOOH@FA-CS drug delivery system: promising targeted anti-tumor drug delivery system with sequential release functions

BackgroundDual loading drug delivery system with tumor targeting efficacy and sequential release function provides a promising platform for anticancer drug delivery. Herein, we established a novel AuCOOH@FACS nanogel system for co-delivery miR-218 mimics (as bio-drug) and Temozolomide(as chemo-drug).MethodsDLS and TEM were employed to determine the characteristics of particles and nanogels. The cell viability was calculated for study synergistic effect of both drugs coadministration and in nanogel forms. The amounts of Au uptake were measured by ICP-MS in cell and tumors to quantify the targeting drug delivery efficacy. Tumor weight and mice weight were investigated to study the targeting antitumor efficacy of nanogel system.ResultsThe results revealed that using AuCOOH@FACS nanogel as delivery vehicles, drugs could be targeting delivery to tumor site, the intracellular uptake is enhanced to a greater extent, and significant antitumor efficacy is fold increase compared with free drug administration group, without noticeable system cytotoxicity.ConclusionsThis system offers an efficient approach to cancer therapy and holds significant potential to improve the treatment of cancer in the future.

Exosome–Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs

Abstract Targeted delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) system to the receptor cells is essential for in vivo gene editing. Exosomes are intensively studied as a promising targeted drug delivery carrier recently, while limited by their low efficiency in encapsulating of large nucleic acids. Here, a kind of hybrid exosomes with liposomes is developed via simple incubation. Different from the original exosomes, the resultant hybrid nanoparticles efficiently encapsulate large plasmids, including the CRISPR–Cas9 expression vectors, similarly as the liposomes. Moreover, the resultant hybrid nanoparticles can be endocytosed by and express the encapsulated genes in the mesenchymal stem cells (MSCs), which cannot be transfected by the liposome alone. Taken together, the exosome–liposome hybrid nanoparticles can deliver CRISPR–Cas9 system in MSCs and thus be promising in in vivo gene manipulation.

Dysregulation of the miR-146a-Smad4 axis impairs osteogenesis of bone mesenchymal stem cells under inflammation

Osteoporosis is a common disease that affects patient quality of life, especially among the elderly population. Although inflammation contributes significantly to osteoporosis, the underlying mechanism is unclear. In this study, we found that tumor necrosis factor (TNF)-α, an inflammatory environment mimic, inhibits osteogenesis of bone mesenchymal stem cells (BMSCs), induces miR-146a and decreases Smad4. Moreover, overexpression of miR-146a inhibited the osteogenic ability of BMSCs, whereas blocking miR-146a partially rescued the osteogenesis deficiency under TNF-α treatment. Molecularly, miR-146a decreased Smad4 expression at the protein level by binding to an element located in the Smad4 3′-untranslated region, and restoration of Smad4 reversed the inhibitory effects of miR-146a on osteogenesis. Together, our results showed that the inflammatory environment mimic TNF-α inhibits osteogenesis via upregulation of miR-146a and subsequent downregulation of Smad4, thus suggesting that therapeutic manipulation of miR-146a maybe a potential strategy to improve osteogenesis in the context of osteoporosis.

The Epigenetic Regulation in Tooth Development and Regeneration

BACKGROUND Tooth loss occurs with age and significantly impacts the quality of elderlys life both physically and psychologically. It has been well known that odontogenesis is a complicated process with sequential and reciprocal interactions between epithelial and mesenchymal tissues and different types of dental tissue-derived stem cells involve in it. However, only a small portion of the intricate mechanisms has been defined nowadays. Among them, epigenetics has become an increasingly important mechanism for tooth development and regeneration. OBJECTIVE This review aims at illustrating the function of epigenetic regulation in odontogenesis, which plays an important role in dental tissue-derived stem cell self-renewal and differentiation nowadays and would be a new strategy for tooth regeneration. RESULTS In this review, we introduced the natural process of tooth development and the functions of stem cells involved in. Furthermore, we summarized the current knowledge on epigenetic regulation including DNA methylation, histone modification, and non-coding RNAs during odontogenesis, providing the theoretical basis for tooth regeneration. CONCLUSION Along with a deeper understanding of odontogenesis, the epigenetic mechanism involved in has become increasingly important. Therefore, its necessary to further study the functions of epigenetic regulation in tooth development and regeneration, which may make tooth regeneration a reality in the future.