RESUMEN
Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects.
Asunto(s)
Materiales Biomiméticos/síntesis química , Bivalvos/química , Neoplasias Óseas/terapia , Regeneración Tisular Dirigida/métodos , Nanoestructuras/administración & dosificación , Fototerapia/métodos , Andamios del Tejido , Animales , Materiales Biocompatibles/síntesis química , Neoplasias Óseas/patología , Línea Celular Tumoral , Cerámica/química , Fracturas del Fémur/patología , Fracturas del Fémur/terapia , Humanos , Nanoestructuras/química , Impresión Tridimensional , ConejosRESUMEN
Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in regenerative medicine in light of their ability to differentiate along the chondrogenic and osteogenic lineages. As a type of traditional Chinese medicine, quercetin has been preliminarily reported to promote osteogenic differentiation in osteoblasts. In the present study, the effects of quercetin on the proliferation, viability, cellular morphology, osteogenic differentiation and angiogenic factor secretion of rat BMSCs (rBMSCs) were examined by MTT assay, fluorescence activated cell sorter (FACS) analysis, real-time quantitative PCR (RT-PCR) analysis, alkaline phosphatase (ALP) activity and calcium deposition assays, and Enzyme-linked immunosorbent assay (ELISA). Moreover, whether mitogen-activated protein kinase (MAPK) signaling pathways were involved in these processes was also explored. The results showed that quercetin significantly enhanced the cell proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in a dose-dependent manner, with a concentration of 2 µM achieving the greatest stimulatory effect. Moreover, the activation of the extracellular signal-regulated protein kinases (ERK) and p38 pathways was observed in quercetin-treated rBMSCs. Furthermore, these induction effects could be repressed by either the ERK inhibitor PD98059 or the p38 inhibitor SB202190, respectively. These data indicated that quercetin could promote the proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in vitro, partially through the ERK and p38 signaling pathways.
Asunto(s)
Inductores de la Angiogénesis/metabolismo , Antioxidantes/farmacología , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Quercetina/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Calcio/metabolismo , Diferenciación Celular/genética , Supervivencia Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/genética , Osteogénesis/genética , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVES: Icariin, a flavonoid isolated from Epimedium pubescens, has previously been identified to exert beneficial effects on preventing bone loss and promoting bone regeneration. However, molecular mechanisms for its anabolic action have, up to now, remained largely unknown. MATERIALS AND METHODS: Effects of icariin on cell proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) were systematically evaluated. To characterize underlying mechanisms, its effects on mitogen-activated protein kinase (MAPK) signalling pathways were determined. RESULTS: Results showed that icariin might not have enhanced effects on cell proliferation. However, it seemed to significantly enhance osteogenic differentiation of BMSCs, demonstrated by increasing alkaline phosphatase (ALP) activity and gene expression of collagen type I (Col I), osteocalcin (OCN) and osteopotin (OPN). It was demonstrated that icariin rapidly phosphorylated extracellular signal-regulated kinase (ERK), p38 kinase and c-Jun N terminal kinase (JNK). Furthermore, icariin-stimulated osteogenic effects on BMSCs were dramatically attenuated by treatment with either specific ERK inhibitor of PD98059, p38 inhibitor of SB202190 or JNK inhibitor SP600125. CONCLUSIONS: These results provide a potential mechanism of anabolic activity of icariin on BMSCs involving ERK, p38 and JNK MAPK pathways.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Medicamentos Herbarios Chinos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/genética , Flavonoides/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Células Madre Mesenquimatosas/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Antracenos/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación del Desarrollo de la Expresión Génica , Imidazoles/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Osteopontina/genética , Osteopontina/metabolismo , Fosforilación/efectos de los fármacos , Cultivo Primario de Células , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVES: Curculigoside, a natural compound isolated from the medicinal plant Curculigo orchioides has been reported to prevent bone loss in ovariectomized rats. However, the underlying molecular mechanisms are largely unknown. This study investigated the effects of curculigoside on proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs). METHODS: The toxicity, proliferation and osteogenic differentiation of BMSCs cultured with various concentrations (0 as control, 10, 100 and 500 µm) of curculigoside were measured by viability assay, MTT analysis, alkaline phosphatase (ALP) activity assay, alizarin red staining and mineralization assay, real-time PCR analysis on osteogenic genes including ALP, type I collagen (Col I), osteocalcin (OCN) and osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2), as well as OPG enzyme-linked immunosorbent assay. KEY FINDINGS: No significant cytotoxicity was observed for BMSCs after supplementation with curculigoside. The proliferation of BMSCs was enhanced after administration of curculigoside, especially 100 µm curculigoside. Moreover, the osteogenic gene expression was significantly enhanced with 100 µm curculigoside treatment. Importantly, curculigoside significantly increased OPG secretion. CONCLUSIONS: The data indicate that curculigoside could promote BMSC proliferation and induce osteogenic differentiation of BMSCs. The most profound response was observed with 100 µm curculigoside. These findings may be valuable for understanding the mechanism of the effect of curculigoside on bone, especially in relation to osteoporosis.