Background/Aims: Osteosarcoma is the predominant form of primary bone malignancy. Although the combinational application of neoadjuvant chemotherapy and surgical resection significantly increases the survival rate, the therapeutic outcome remains unsatisfactory. Deoxyelephantopin (DET), an active ingredient of Elephantopus scaber, has been reported to have an anti-tumor effect in recent publications. This study aimed to investigate whether DET has antineoplastic effects on osteosarcoma cells and its underlying mechanism. Methods: Cell viability and morphological changes were assessed by MTT and Live/dead assays. Cell apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were detected utilizing Annexin V-FITC/PI double staining, DCFH-DA and JC-1 probes, respectively. Autophagy was detected by mRFP-GFP-LC3 adenovirus transfection and western blot. Results: DET dose-dependently reduced the viability of osteosarcoma cells following the increase in intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) reversed this effect. Furthermore, DET induced mitochondrial apoptosis. Depolarized cells were increased, and apoptosis-related proteins, such as Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3 and cleaved ploy ADP-ribose polymerase, were activated. Additionally, we found that DET could induce autophagy in osteosarcoma cells, but autophagy inhibition did not affect the decrease in cell viability. Conclusion: DET induced apoptosis in osteosarcoma cells through ROS generation, mitochondrial dysfunction and caspase activation; in addition, autophagy was involved in the effects of DET on osteosarcoma cells.
Background and Purpose The extracellular matrix (ECM) derived from bone marrow mesenchymal stem cells (BMSCs) has been used in regenerative medicine because of its good biological activity; however, its poor mechanical properties limit its application in bone regeneration. The purpose of this study is to construct a three dimensional-printed hydroxyapatite (3D-HA)/BMSC-ECM composite scaffold that not only has biological activity but also sufficient mechanical strength and reasonably distributed spatial structure. Methods A BMSC-ECM was first extracted and formed into micron-sized particles, and then the ECM particles were modified onto the surface of 3D-HA scaffolds using an innovative linking method to generate composite 3D-HA/BMSC-ECM scaffolds. The 3D-HA scaffolds were used as the control group. The basic properties, biocompatibility and osteogenesis ability of both scaffolds were tested in vitro. Finally, a critical skull defect rat model was created and the osteogenesis effect of the scaffolds was evaluated in vivo. Results The compressive modulus of the composite scaffolds reached 9.45±0.32 MPa, which was similar to that of the 3D-HA scaffolds ( p >0.05). The pore size of the two scaffolds was 305±47 um and 315±34 um ( p >0.05), respectively. A CCK-8 assay indicated that the scaffolds did not have cytotoxicity. The composite scaffolds had good cell adhesion ability, with a cell adhesion rate of up to 76.00±6.17% after culturing for 7 hours, while that of the 3D-HA scaffolds was 51.85±4.77% ( p <0.01). In addition, the composite scaffold displayed higher alkaline phosphatase (ALP) activity, osteogenesis-related mRNA expression, and calcium nodule formation, thus confirming that the composite scaffolds had good osteogenic activity. The composite scaffolds exhibited good bone repair in vivo and were superior to the 3D-HA scaffolds. Conclusion We conclude that BMSC-ECM is a good osteogenic material and that the composite scaffolds have good osteogenic ability, which provides a new method and concept for the repair of bone defects.
Bone marrow mesenchymal stem cells (BMSCs) are a potential source of osteoblasts and have been widely used in clinical therapies due to their pluripotency. Recent publications have found that resveratrol (RSVL) played a crucial role in the proliferation and differentiation of BMSCs; however, the underlying molecular mechanism of RSVL‐induced BMSCs osteogenic differentiation needs to be fully elucidated. The objective of this study was to explore functions of miRNAs in the RSVL‐treated BMSCs and its effects on the differentiation potentials of BMSCs. The findings demonstrated that RSVL enhanced the osteogenesis and suppressed the adipogenesis of BMSCs in a dose‐dependent manner. Besides, a novel regulatory axis containing miR‐320c, and its target Runx2 was found during the differentiation process of BMSCs under RSVL treatment. Increase of miR‐320c reduced the osteogenic potential of BMSCs, while knockdown of miR‐320c played a positive role in the osteogenesis of BMSCs. In contrast, overexpression of miR‐320c accelerated the adipogenic differentiation, while knockdown of miR‐320c restrained the adipogenic differentiation of BMSCs. The results confirmed that Runx2 might be the direct target of miR‐320c in RSVL‐promoted osteogenic differentiation of BMSCs. This study revealed that RSVL might be used for the treatment of bone loss related diseases and miR‐320c could be regarded as a novel and potential target to regulate the biological functions of BMSCs.
The extracellular matrix(ECM), which is primarily composed of collagens and proteoglycans, plays a key role in cell proliferation, differentiation, and migration and interactions between cells. In this study, we produced chitosan/gelatin/bone marrow stem cells-derived extracellular matrix(C/G/BMSCs-dECM) scaffolds via lyophilization and cross-linking, and chitosan/gelatin(C/G) scaffolds were used as controls. For the C/G/BMSCs-dECM scaffolds, the average pore size was 289.17 ± 80.28 μm; the average porosity was 89.25 ± 3.75%; the average compressive modulus was 0.82 ± 0.07 MPa; and the average water uptake ratio was 13.81 ± 1.00. In vitro, the C/G/BMSCs-dECM scaffolds promoted bone marrow stem cells(BMSCs) attachment and proliferation. Moreover, improved osteogenic differentiation was observed for these scaffolds. Thus, C/G/BMSCs-dECM is a promising material for bone tissue engineering.
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