Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human...Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling.This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.展开更多
The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease...The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease(DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate(EP) and annulus fibrosus(AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol(2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.展开更多
Phytocyanin(PC)is a class of plant-specific blue copper proteins involved in electron transport,plant growth,development,and stress resistance.However,PC proteins have not been systematically evaluated in tobacco plan...Phytocyanin(PC)is a class of plant-specific blue copper proteins involved in electron transport,plant growth,development,and stress resistance.However,PC proteins have not been systematically evaluated in tobacco plants.We determined the whole-genome sequences of the PC family in the tobacco cultivar‘K326.’The transcriptome data were used to analyze the expression of the NtPC family at different development stages and tissue-specific genes.Real-time fluorescence quantitative analysis was used to analyze the expression of the NtPC gene family under low temperature and methyl jasmonate stress.The tobacco NtPC family contained 110 members and was divided into four subfamilies:early nodulin-like protein(NtENODL),uclacyanin-like protein,stellacyanin1-like protein,and plantacyanin-like protein.According to phylogenetic and structural analyses,the NtPC family could be divided into eight structural types.Fifty-three NtPCs were randomly distributed on 22 of 24 tobacco chromosomes.Collinearity analysis revealed 33 pairs of genes belonging to the NtPC family.Gene ontology analysis showed that the PC genes are components of the plasma membrane and may participate in plasma membrane-related functions.The NtPC family contained numerous elements related to hormonal and abiotic stress responses and was specifically expressed in the tobacco prosperous,maturation,and budding periods.Tissue-specific expression analysis showed that some genes were tissue specific.The expression of NtENODL58 and other genes was significantly induced by low-temperature and methyl jasmonate stress.Thus,the NtPC gene family plays an important role in plant stress response.展开更多
基金supported by the National Key Research and Development Program of China (2018YFA0800802)the National Natural Science Foundation of China (No. 81530071+5 种基金No. 31571382No. 81871817)the Key Project of Innovation Program in Military Medicine (16CXZ016)the Sports Scientific Research Project of Chongqing (B201801)the Basic and Advanced Research Project in Chongqing (cstc2017jcyjAX0148)the Project of the State Key Laboratory of Trauma, Burns and Combined Injury (No. SKLZZ(Ⅲ)201601)。
文摘Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling.This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.
基金supported by grants from the National Key Research and Development Program of China (2018YFA0800802)the National Natural Science Foundation of China (81830075, 81772306, 81530071, and 81991513)the Chongqing Talent Plan (CQYC202001008 and CQYC202005088)
文摘The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease(DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate(EP) and annulus fibrosus(AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol(2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.
基金This study was supported by the Tobacco Science Research Institute of the Chongqing Tobacco Company(A20201NY01-1305).
文摘Phytocyanin(PC)is a class of plant-specific blue copper proteins involved in electron transport,plant growth,development,and stress resistance.However,PC proteins have not been systematically evaluated in tobacco plants.We determined the whole-genome sequences of the PC family in the tobacco cultivar‘K326.’The transcriptome data were used to analyze the expression of the NtPC family at different development stages and tissue-specific genes.Real-time fluorescence quantitative analysis was used to analyze the expression of the NtPC gene family under low temperature and methyl jasmonate stress.The tobacco NtPC family contained 110 members and was divided into four subfamilies:early nodulin-like protein(NtENODL),uclacyanin-like protein,stellacyanin1-like protein,and plantacyanin-like protein.According to phylogenetic and structural analyses,the NtPC family could be divided into eight structural types.Fifty-three NtPCs were randomly distributed on 22 of 24 tobacco chromosomes.Collinearity analysis revealed 33 pairs of genes belonging to the NtPC family.Gene ontology analysis showed that the PC genes are components of the plasma membrane and may participate in plasma membrane-related functions.The NtPC family contained numerous elements related to hormonal and abiotic stress responses and was specifically expressed in the tobacco prosperous,maturation,and budding periods.Tissue-specific expression analysis showed that some genes were tissue specific.The expression of NtENODL58 and other genes was significantly induced by low-temperature and methyl jasmonate stress.Thus,the NtPC gene family plays an important role in plant stress response.