Traditional serrated adenoma(TSA)is a type of serrated polyp of the colorectum and is thought to be a precancerous lesion.There are three types of serrated polyps,namely,hyperplastic polyps,sessile serrated adenomas/p...Traditional serrated adenoma(TSA)is a type of serrated polyp of the colorectum and is thought to be a precancerous lesion.There are three types of serrated polyps,namely,hyperplastic polyps,sessile serrated adenomas/polyps,and TSAs.TSA is the least common of the three types and accounts for about 5% of serrated polyps.Here we report a pediatric case of TSA that was successfully resected by endoscopic submucosal dissection(ESD).This rare case report describes a pediatric patient with no family history of colonic polyp who was admitted to our hospital with hematochezia.On colonoscopy,we found a polypoid lesion measuring 10 mm in diameter in the lower rectum.We selected ESD as a surgical option for en bloc resection,and histopathological examination revealed TSA.The findings in this case suggest that TSA with precancerous potential can occur in children,and that ESD is useful for treating this lesion.展开更多
Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming osteoblasts.Recent studies have shown that...Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming osteoblasts.Recent studies have shown that histone demethylases are implicated in osteoblastogenesis;however,little is known about the role of histone demethylases in osteoclast formation.Here,we identified KDM4B as an epigenetic regulator of osteoclast differentiation.Knockdown of KDM4B significantly blocked the formation of tartrate-resistant acid phosphatase-positive multinucleated cells.Mice with myeloid-specific conditional knockout of KDM4B showed an osteopetrotic phenotype due to osteoclast deficiency.Biochemical analysis revealed that KDM4B physically and functionally associates with CCAR1 and MED1 in a complex.Using genome-wide chromatin immunoprecipitation(ChIP)-sequencing,we revealed that the KDM4B–CCAR1–MED1 complex is localized to the promoters of several osteoclast-related genes upon receptor activator of NF-κB ligand stimulation.We demonstrated that the KDM4B–CCAR1–MED1 signaling axis induces changes in chromatin structure(euchromatinization)near the promoters of osteoclast-related genes through H3K9 demethylation,leading to NF-κB p65 recruitment via a direct interaction between KDM4B and p65.Finally,small molecule inhibition of KDM4B activity impeded bone loss in an ovariectomized mouse model.Taken together,our findings establish KDM4B as a critical regulator of osteoclastogenesis,providing a potential therapeutic target for osteoporosis.展开更多
文摘Traditional serrated adenoma(TSA)is a type of serrated polyp of the colorectum and is thought to be a precancerous lesion.There are three types of serrated polyps,namely,hyperplastic polyps,sessile serrated adenomas/polyps,and TSAs.TSA is the least common of the three types and accounts for about 5% of serrated polyps.Here we report a pediatric case of TSA that was successfully resected by endoscopic submucosal dissection(ESD).This rare case report describes a pediatric patient with no family history of colonic polyp who was admitted to our hospital with hematochezia.On colonoscopy,we found a polypoid lesion measuring 10 mm in diameter in the lower rectum.We selected ESD as a surgical option for en bloc resection,and histopathological examination revealed TSA.The findings in this case suggest that TSA with precancerous potential can occur in children,and that ESD is useful for treating this lesion.
基金support of the National Research Foundation of Korea(2017R1C1B2008017,2020R1A6A1A06046235,and 2020R1A2C1008179 to K.K.,2019R1I1A1A01061125 to S.J.Y.).
文摘Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming osteoblasts.Recent studies have shown that histone demethylases are implicated in osteoblastogenesis;however,little is known about the role of histone demethylases in osteoclast formation.Here,we identified KDM4B as an epigenetic regulator of osteoclast differentiation.Knockdown of KDM4B significantly blocked the formation of tartrate-resistant acid phosphatase-positive multinucleated cells.Mice with myeloid-specific conditional knockout of KDM4B showed an osteopetrotic phenotype due to osteoclast deficiency.Biochemical analysis revealed that KDM4B physically and functionally associates with CCAR1 and MED1 in a complex.Using genome-wide chromatin immunoprecipitation(ChIP)-sequencing,we revealed that the KDM4B–CCAR1–MED1 complex is localized to the promoters of several osteoclast-related genes upon receptor activator of NF-κB ligand stimulation.We demonstrated that the KDM4B–CCAR1–MED1 signaling axis induces changes in chromatin structure(euchromatinization)near the promoters of osteoclast-related genes through H3K9 demethylation,leading to NF-κB p65 recruitment via a direct interaction between KDM4B and p65.Finally,small molecule inhibition of KDM4B activity impeded bone loss in an ovariectomized mouse model.Taken together,our findings establish KDM4B as a critical regulator of osteoclastogenesis,providing a potential therapeutic target for osteoporosis.
