Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
Core decompression(CD)with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head(ONFH).Adjuvant treatments are widely used in combina...Core decompression(CD)with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head(ONFH).Adjuvant treatments are widely used in combination with CD as suitable methods of therapy.Existing augmentations have to be fabricated in advance.Here,we report a novel injectable glycerin-modified polycaprolactone(GPCL)that can adapt to the shape of the CD cavity.GPCL shows great flowability at 52.6℃.After solidification,its compressive modulus was 120 kPa at body temperature(37℃).This excellent characteristic enables the polymer to provide mechanical support in vivo.In addition,GPCL acts as a carrier of the therapeutic agent zoledronic acid(ZA),demonstrating sustained release into the CD region.ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases.Compared to that in the CD group,CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head.At the interface between the GPCL and CD tunnel wall,osteogenesis was significantly promoted.In addition,morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance.These results suggest a strategy effective to preserve the bone density of the femoral head,thus decreasing the possibility of femoral head collapse.This novel injectable polymer has,therefore,considerable potential in clinical applications.展开更多
基金the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
基金supported by the National Natural Science Foundation of China(NSFC:81672173,82072448)the Key Research Development Program of Shaanxi Province(2018ZDCXL-SF-28-7)。
文摘Core decompression(CD)with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head(ONFH).Adjuvant treatments are widely used in combination with CD as suitable methods of therapy.Existing augmentations have to be fabricated in advance.Here,we report a novel injectable glycerin-modified polycaprolactone(GPCL)that can adapt to the shape of the CD cavity.GPCL shows great flowability at 52.6℃.After solidification,its compressive modulus was 120 kPa at body temperature(37℃).This excellent characteristic enables the polymer to provide mechanical support in vivo.In addition,GPCL acts as a carrier of the therapeutic agent zoledronic acid(ZA),demonstrating sustained release into the CD region.ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases.Compared to that in the CD group,CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head.At the interface between the GPCL and CD tunnel wall,osteogenesis was significantly promoted.In addition,morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance.These results suggest a strategy effective to preserve the bone density of the femoral head,thus decreasing the possibility of femoral head collapse.This novel injectable polymer has,therefore,considerable potential in clinical applications.
