Pluripotent mesenchymal stem cells (MSCs) are bone marrow stromal progenitor cells that can differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. Several signaling pathways have been shown to regulate the lineage commitment and terminal differentiation of MSCs. Here, we conducted a comprehensive analysis of the 14 types of bone morphogenetic protein (BMPs) for their abilities to regulate multilineage specific differentiation of MSCs. We found that most BMPs exhibited distinct abilities to regulate the expression of Runx2, Sox9, MyoD, and PPARγ2. Further analysis indicated that BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 effectively induced both adipogenic and osteogenic differentiation in vitro and in vivo. BMP-induced commitment to osteogenic or adipogenic lineage was shown to be mutually exclusive. Overexpression of Runx2 enhanced BMP-induced osteogenic differentiation, whereas knockdown of Runx2 expression diminished BMP-induced bone formation with a decrease in adipocyte accumulation in vivo. Interestingly, overexpression of PPARγ2 not only promoted adipogenic differentiation, but also enhanced osteogenic differentiation upon BMP-2, BMP-6, and BMP-9 stimulation. Conversely, MSCs with PPARγ2 knockdown or mouse embryonic fibroblasts derived from PPARγ2^−/− mice exhibited a marked decrease in adipogenic differentiation, coupled with reduced osteogenic differentiation and diminished mineralization upon BMP-9 stimulation, suggesting that PPARγ2 may play a role in BMP-induced osteogenic and adipogenic differentiation. Thus, it is important to understand the molecular mechanism behind BMP-regulated lineage divergence during MSC differentiation, as this knowledge could help us to understand the pathogenesis of skeletal diseases and may lead to the development of strategies for regenerative medicine.

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS₂) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS₂ nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS₂-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS₂-PEG nanoflakes under the irradiation. These results thus suggest that the MoS₂-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

A drug-loaded implantable scaffold is a promising alternative for the treatment of a tissue defect after tumor resection. In this study, mesoporous silica nanoparticles (MSNs) were used as carriers to load an anticancer drug – doxorubicin hydrochloride (DOX), and the DOX-loaded MSNs (DOX@MSNs) were subsequently incorporated into poly(L-lactic acid) (PLLA) nanofibers via electrospinning, resulting in a new drug-loaded nanofibrous scaffold (PLLA/DOX@MSNs). The as-prepared composite nanofibrous scaffold was characterized by various techniques. In vitro release profiles of DOX from PLLA/DOX@MSNs composite nanofibers were examined and the in vitro antitumor efficacy against HeLa cells was also evaluated. The results showed that DOX-loaded MSNs were successfully incorporated into composite nanofibers with different MSN (or DOX) contents. Among them, the PLLA/1.0% DOX@10% MSN nanofibers exhibited good particle distribution and improved thermal stability. More importantly, they possessed high DOX-loading capacities due to which the drug can be released in a sustained and prolonged manner, and therefore higher in vitro antitumor efficacy than their MSNs-free counterparts. Thus, the prepared PLLA/MSNs composite nanofibrous mats are highly promising as local implantable scaffolds for potential postsurgical cancer treatment.