Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells tha...Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells.The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) prognosis.The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay.The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay.KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM.Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells.Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo.Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation.Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.展开更多
Mesenchymal stem cells, due to their characteristics are ideal candidates for cellular therapy. Currently, in culture these cells are defined by their adherence to plastic, specific surface antigen expression and mult...Mesenchymal stem cells, due to their characteristics are ideal candidates for cellular therapy. Currently, in culture these cells are defined by their adherence to plastic, specific surface antigen expression and multipotent differentiation potential. However, the in vivo identification of mesenchymal stem cells, before culture, is not so well established. Pre-culture identification markers would ensure higher purity than that obtained with selection based on adherence to plastic. Up until now, CD271 has been described as the most specific marker for the characterization andpurification of human bone marrow mesenchymal stem cells. This marker has been shown to be specifically expressed by these cells. Thus, CD271 has been proposed as a versatile marker to selectively isolated and expand multipotent mesenchymal stem cells with both immunosuppressive and lymphohematopoietic engraftment-promoting properties. This review focuses on this marker, specifically on identification of mesenchymal stem cells from different tissues. Literature revision suggests that CD271 should not be defined as a universal marker to identify mesenchymal stem cells before culture from different sources. In the case of bone marrow or adipose tissue, CD271 could be considered a quite suitable marker; however this marker seems to be inadequate for the isolation of mesenchymal stem cells from other tissues such as umbilical cord blood or wharton's jelly among others.展开更多
BACKGROUND Accumulating evidence suggests that the maxillary process,to which cranial crest cells migrate,is essential to tooth development.Emerging studies indicate that Cd271 plays an essential role in odontogenesis...BACKGROUND Accumulating evidence suggests that the maxillary process,to which cranial crest cells migrate,is essential to tooth development.Emerging studies indicate that Cd271 plays an essential role in odontogenesis.However,the underlying mechanisms have yet to be elucidated.AIM To establish the functionally heterogeneous population in the maxillary process,elucidate the effects of Cd271 deficiency on gene expression differences.METHODS p75NTR knockout(Cd271-/-)mice(from American Jackson laboratory)were used to collect the maxillofacial process tissue of p75NTR knockout mice,and the wildtype maxillofacial process of the same pregnant mouse wild was used as control.After single cell suspension,the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system.Finally,the sequencing data in Fastq format were obtained.The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data.The gene expression matrix is read by R software,and Seurat is used to control and standardize the data,reduce the dimension and cluster.We search for marker genes for subgroup annotation by consulting literature and database;explore the effect of p75NTR knockout on mesenchymal stem cells(MSCs)gene expression and cell proportion by cell subgrouping,differential gene analysis,enrichment analysis and protein-protein interaction network analysis;understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis.Last we verified the findings single cell sequencing in vitro.RESULTS We identified 21 cell clusters,and we re-clustered these into three subclusters.Importantly,we revealed the cell–cell communication networks between clusters.We clarified that Cd271 was significantly associated with the regulation of mineralization.CONCLUSION This study provides comprehensive mechanistic insights into the maxillary-process-derived MSCs and demonstrates that Cd271 is significantly associated with the odontogenesis in mesenchymal populations.展开更多
With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritisrepresents a multifactorial disease with no effective treatment options. As biomechanical shift in t...With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritisrepresents a multifactorial disease with no effective treatment options. As biomechanical shift in thetrabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delayOA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models.We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and painsensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase insubchondral bone volume and trabecular thickness with constant bone mineral density was found indicatingfavored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in controlsamples without magnesium. However, this result could not be confirmed by sensitive, objective lamenessevaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degenerationevaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented resultsshow a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevanceregarding pain. Further studies with shifted focus should examine additional structures as joint capsule orosteophytes.展开更多
基金supported by grants from the Ministry of Science and Technology of China (Grant No.2015CB931804)National Natural Science Foundation of China (Grant No.U1505225, 81773063, 81273548, 81571802)+1 种基金the Natural Science Foundation of Fujian Province (Grant No.2016J06020)Fujian Development and Reform Commission project (Grant No.829054)
文摘Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells.The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) prognosis.The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay.The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay.KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM.Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells.Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo.Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation.Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.
文摘Mesenchymal stem cells, due to their characteristics are ideal candidates for cellular therapy. Currently, in culture these cells are defined by their adherence to plastic, specific surface antigen expression and multipotent differentiation potential. However, the in vivo identification of mesenchymal stem cells, before culture, is not so well established. Pre-culture identification markers would ensure higher purity than that obtained with selection based on adherence to plastic. Up until now, CD271 has been described as the most specific marker for the characterization andpurification of human bone marrow mesenchymal stem cells. This marker has been shown to be specifically expressed by these cells. Thus, CD271 has been proposed as a versatile marker to selectively isolated and expand multipotent mesenchymal stem cells with both immunosuppressive and lymphohematopoietic engraftment-promoting properties. This review focuses on this marker, specifically on identification of mesenchymal stem cells from different tissues. Literature revision suggests that CD271 should not be defined as a universal marker to identify mesenchymal stem cells before culture from different sources. In the case of bone marrow or adipose tissue, CD271 could be considered a quite suitable marker; however this marker seems to be inadequate for the isolation of mesenchymal stem cells from other tissues such as umbilical cord blood or wharton's jelly among others.
基金National Natural Science Foundation of China(General Program),No.31870971Medical Health Science and Technology Project of Zhejiang Province,No.2023KY155.
文摘BACKGROUND Accumulating evidence suggests that the maxillary process,to which cranial crest cells migrate,is essential to tooth development.Emerging studies indicate that Cd271 plays an essential role in odontogenesis.However,the underlying mechanisms have yet to be elucidated.AIM To establish the functionally heterogeneous population in the maxillary process,elucidate the effects of Cd271 deficiency on gene expression differences.METHODS p75NTR knockout(Cd271-/-)mice(from American Jackson laboratory)were used to collect the maxillofacial process tissue of p75NTR knockout mice,and the wildtype maxillofacial process of the same pregnant mouse wild was used as control.After single cell suspension,the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system.Finally,the sequencing data in Fastq format were obtained.The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data.The gene expression matrix is read by R software,and Seurat is used to control and standardize the data,reduce the dimension and cluster.We search for marker genes for subgroup annotation by consulting literature and database;explore the effect of p75NTR knockout on mesenchymal stem cells(MSCs)gene expression and cell proportion by cell subgrouping,differential gene analysis,enrichment analysis and protein-protein interaction network analysis;understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis.Last we verified the findings single cell sequencing in vitro.RESULTS We identified 21 cell clusters,and we re-clustered these into three subclusters.Importantly,we revealed the cell–cell communication networks between clusters.We clarified that Cd271 was significantly associated with the regulation of mineralization.CONCLUSION This study provides comprehensive mechanistic insights into the maxillary-process-derived MSCs and demonstrates that Cd271 is significantly associated with the odontogenesis in mesenchymal populations.
基金funded by the German Research Foundation(Deutsche Forschungsgesellschaft,DFG,grant numbers 404534760).
文摘With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritisrepresents a multifactorial disease with no effective treatment options. As biomechanical shift in thetrabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delayOA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models.We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and painsensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase insubchondral bone volume and trabecular thickness with constant bone mineral density was found indicatingfavored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in controlsamples without magnesium. However, this result could not be confirmed by sensitive, objective lamenessevaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degenerationevaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented resultsshow a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevanceregarding pain. Further studies with shifted focus should examine additional structures as joint capsule orosteophytes.
