BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutat...BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.展开更多
Objective To investigate the effects of nivalenol(NIV) and selenium(Se) on the metabolism of aggrecan in the cultured chondrocytes,and to explore the mechanism involved in cartilage aggrecan catabolism in the process ...Objective To investigate the effects of nivalenol(NIV) and selenium(Se) on the metabolism of aggrecan in the cultured chondrocytes,and to explore the mechanism involved in cartilage aggrecan catabolism in the process of Kashin-Beck Disease(KBD).Method Aggrecan mRNA expression was studied by RT-PCR.The concentration of GlcUA in culture medium was determined by diphenylenimine-sulfuric acid method.Result NIV significantly decrease aggrecan mRNA expression.That Se can partially antagonize the effect of NIV on aggrecan mRNA expression.The content of GlcUA in medium with NIV was high er than that in other groups.Conclusion NIV could inhibit chondrocyte synthesis aggrecan,promote the loss of aggrecan from cartilage.All the effects result in the metabolic disorder of the cartilage aggrecan,which eventually leads to irreversible mechani cal destruction of the cartilage.It suggested that Se can partially alleviate the effects of NIV on chondrocytes cultured in vitro.展开更多
From this article,we can find that nivalenol could damage the DNA,disturb aggrecan mRNA expression in chondro cytes and further induce metabolic disturbance of cartilage extracellular matrix,which may play an importan...From this article,we can find that nivalenol could damage the DNA,disturb aggrecan mRNA expression in chondro cytes and further induce metabolic disturbance of cartilage extracellular matrix,which may play an important role during patho genesis of KBD.Se supplementation can resist the injury of nivalenol to chondrocytes,but its action is limited.展开更多
目的:观察独活寄生汤血清对膝骨性关节炎退变软骨细胞Aggrecan和Collagen X mRNA表达的影响。方法:选择6例患者标本均来源于云南省中医医院骨科膝骨性关节炎住院患者,行手术截取的新鲜退变软骨组织,采用组织块法培养原代细胞;MTT法检测...目的:观察独活寄生汤血清对膝骨性关节炎退变软骨细胞Aggrecan和Collagen X mRNA表达的影响。方法:选择6例患者标本均来源于云南省中医医院骨科膝骨性关节炎住院患者,行手术截取的新鲜退变软骨组织,采用组织块法培养原代细胞;MTT法检测传代第一代细胞生长情况,并绘制生长曲线;制备独活寄生汤大鼠含药血清;均取传代第一代的退变软骨细胞,配制5%、10%、20%独活寄生汤含药血清及相应体积比浓度的生理盐水血清作为对照;MTT法检测不同浓度的独活寄生汤血清对退变软骨细胞增殖的影响;实时荧光定量PCR检测不同给药时间点各组退变软骨细胞Aggrecan和Collagen Ⅹ mRNA的表达。结果:退变软骨细胞传代第一代生长曲线见传代第8天时细胞增殖达到顶峰,故选择细胞传代第8天为给药干预时间点;与含同体积比的生理盐水血清组比较,不同浓度的独活寄生汤血清可对退变软骨细胞增殖产生促进作用(P<0.01),尤以10%独活寄生汤血清更为明显(P<0.05);与含同体积比生理盐水血清组比较,不同时间点的5%、10%、20%独活寄生汤血清干预后的退变软骨细胞Aggrecan mRNA的表达均上调(P<0.01),Collagen Ⅹ mRNA的表达均下调(P<0.01),且以10%独活寄生汤血清组的作用最为明显(P<0.05)。结论:独活寄生汤可能通过调节退变软骨组织的胶原及其蛋白多糖的表达而产生延缓膝骨性关节炎退变软骨组织的部分作用。展开更多
文摘BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.
基金supported by the Scientific and Technological Research Project of the Education Department of Shaanxi Province(12JK0703)the Natural Science Foundation of Shaanxi Provincial Health Department(2012D75)foundation of Xi'an Medical University(11FZ26)
文摘Objective To investigate the effects of nivalenol(NIV) and selenium(Se) on the metabolism of aggrecan in the cultured chondrocytes,and to explore the mechanism involved in cartilage aggrecan catabolism in the process of Kashin-Beck Disease(KBD).Method Aggrecan mRNA expression was studied by RT-PCR.The concentration of GlcUA in culture medium was determined by diphenylenimine-sulfuric acid method.Result NIV significantly decrease aggrecan mRNA expression.That Se can partially antagonize the effect of NIV on aggrecan mRNA expression.The content of GlcUA in medium with NIV was high er than that in other groups.Conclusion NIV could inhibit chondrocyte synthesis aggrecan,promote the loss of aggrecan from cartilage.All the effects result in the metabolic disorder of the cartilage aggrecan,which eventually leads to irreversible mechani cal destruction of the cartilage.It suggested that Se can partially alleviate the effects of NIV on chondrocytes cultured in vitro.
基金supported by the Scientific and Technological Research Project of the Education Department of Shaanxi Province(12JK0703)the Natural Science Foundation of Shaanxi Provincial Health Department(2012D75)the foundation of Xi’an Medical University(11FZ26)
文摘From this article,we can find that nivalenol could damage the DNA,disturb aggrecan mRNA expression in chondro cytes and further induce metabolic disturbance of cartilage extracellular matrix,which may play an important role during patho genesis of KBD.Se supplementation can resist the injury of nivalenol to chondrocytes,but its action is limited.
