Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and ...Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.展开更多
Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions.In this study,we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheum...Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions.In this study,we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis(RA).Arthritic mice displayed fracture nonunion with the absence of fracture callus,diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties,representing the major manifestations of atrophic nonunion in the clinic.Mechanistically,we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes,as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro.In this regard,we developed a biodegradable scaffold loaded with SPP1 and CXCL12,which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation.Hence,these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.展开更多
基金This work was supported by the China Postdoctoral Science Foundation under grant No.2004035588.
文摘Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.
基金supported by the following NIH/NIAMS grants:R01 grants(AR075860 and AR077616 to J.S.,AR072623 and AR049192 to Y.A.EB022018,HL138175,HL138353,AG056919,and AR077616 to J.G.),an R21 grant(AR077226 to J.S.),a P30 Core Center grant(AR074992 to the Musculoskeletal Research Center)a biomedical grant from Shriners Hospital for Children(#85160 to Y.A.).
文摘Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions.In this study,we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis(RA).Arthritic mice displayed fracture nonunion with the absence of fracture callus,diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties,representing the major manifestations of atrophic nonunion in the clinic.Mechanistically,we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes,as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro.In this regard,we developed a biodegradable scaffold loaded with SPP1 and CXCL12,which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation.Hence,these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.
