OBJECTIVE: To investigate the effects of Ermiao Fang(EM) with medical guide Xixin(Herba Asari Mandshurici)(HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis(OA) rats.METHODS: OA rats were induc...OBJECTIVE: To investigate the effects of Ermiao Fang(EM) with medical guide Xixin(Herba Asari Mandshurici)(HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis(OA) rats.METHODS: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups.All rats were injected with recombinant human granulocyte colony-stimulating factor 30μg·kg-1·d-1for7 days and treated with EMor EM plus HAM at 1.6 or 1.9 g·kg-1·d-1 for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta(IL-1β) tumor necrosis factor alpha(TNF-α) nitric oxide(NO), and inducible nitric oxide synthase(iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases(MMPs)-13,tissue inhibitors of metalloproteinases(TIMPs)-1,Bromodeoxyuridine(BrdU), cluster of differentiation 34(CD34), and stromal cell-derived factor 1(SDF-1) were measured by immunohistochemical assay.RESULTS:The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group.The EM and EMplus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1β, TNF-α, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34,and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects.CONCLUSION: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone.展开更多
基金Supported by Grants from the National Natural Science Foundation of China Project of Guiding Traditional Chinese Medicine Induced Bone Marrow Stem Cell Directional Homing to a Focal Zone for the Treatment of Osteoarthritis(No.81072900)
文摘OBJECTIVE: To investigate the effects of Ermiao Fang(EM) with medical guide Xixin(Herba Asari Mandshurici)(HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis(OA) rats.METHODS: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups.All rats were injected with recombinant human granulocyte colony-stimulating factor 30μg·kg-1·d-1for7 days and treated with EMor EM plus HAM at 1.6 or 1.9 g·kg-1·d-1 for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta(IL-1β) tumor necrosis factor alpha(TNF-α) nitric oxide(NO), and inducible nitric oxide synthase(iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases(MMPs)-13,tissue inhibitors of metalloproteinases(TIMPs)-1,Bromodeoxyuridine(BrdU), cluster of differentiation 34(CD34), and stromal cell-derived factor 1(SDF-1) were measured by immunohistochemical assay.RESULTS:The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group.The EM and EMplus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1β, TNF-α, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34,and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects.CONCLUSION: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone.