RESUMEN
Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 µg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.
Asunto(s)
Enfermedades Óseas , Exosomas , Prunus domestica , Animales , Ratones , Osteoclastos , Osteoblastos , Diferenciación CelularRESUMEN
Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the digestive tract that causes pain and weight loss and also increases the risk of colon cancer. Inspired by the benefits of plant-derived nanovesicles and aloe, we herein report aloe-derived nanovesicles, including aloe vera-derived nanovesicles (VNVs), aloe arborescens-derived nanovesicles (ANVs), and aloe saponaria-derived nanovesicles (SNVs) and evaluate their therapeutic potential and molecular mechanisms in a dextran sulfate sodium (DSS)-induced acute experimental colitis mouse model. Aloe-derived nanovesicles not only facilitate markedly reduced DSS-induced acute colonic inflammation, but also enable the restoration of tight junction (TJ) and adherent junction (AJ) proteins to prevent gut permeability in DSS-induced acute colonic injury. These therapeutic effects are ascribed to the anti-inflammatory and anti-oxidant effects of aloe-derived nanovesicles. Therefore, aloe-derived nanovesicles are a safe treatment option for IBD.
Asunto(s)
Aloe , Colitis , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Aloe/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Modelos Animales de Enfermedad , Sulfato de Dextran , Ratones Endogámicos C57BLRESUMEN
SCOPE: Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a chronic recurrent inflammatory disease of the digestive tract and increases the risk of colon cancer. METHOD AND RESULTS: This study evaluates the effects of dietary intervention with freeze-dried plum (FDP), a natural antioxidant and anti-inflammatory fruit with no toxicity on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in a mouse model and studies the molecular mechanisms of protection through the gut-liver axis. The results show that FDP decreases the levels of inflammatory mediators, which is a nitrative stress biomarker in both acute and chronic models. FDP markedly reduces DSS-induced injury to the colonic epithelium in both acute and chronic models. In addition, FDP significantly decreases the levels of pro-oxidant markers such as CYP2E1, iNOS, and nitrated proteins (detected by anti-3-NT antibody) in DSS-induced acute and chronic colonic injury models. Furthermore, FDP markedly reduces markers of liver injury such as serum ALT/AST, antioxidant markers, and inflammatory mediators in DSS-induced acute and chronic colonic injury. CONCLUSION: These results demonstrate that the FDP exhibits a protective effect on DSS-induced acute and chronic colonic and liver injury through the gut-liver axis via antioxidant and anti-inflammatory properties.