Background and objective:Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors.A variety of genetic factors have been reported,whereas few investigations have focused on epigen...Background and objective:Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors.A variety of genetic factors have been reported,whereas few investigations have focused on epigenetic regulation during liver regeneration.In the present study,valproic acid(VPA),a histone deacetylase(HDAC) inhibitor,was used to investigate the effect of HDAC on liver regeneration.Methods:VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration.The mice were sacrificed,and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment.DNA synthesis was detected via a BrdU assay,and cell proliferation was tested using Ki-67.The expressions of cyclin D1,cyclin E,cyclin dependent kinase 2(CDK2),and CDK4 were detected by Western blot analysis.Chromatin immunoprecipitation(ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot.Results:Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased,and the peak of BrdU was delayed in the VPA-administered mice.Consistently,cyclin D1 expression was also delayed.We identified B-myc as a target gene of HDACs by complementary DNA(cDNA) microarray.The expression of B-myc increased in the VPA-administered mice after hepatectomy(PH).The ChIP assay confirmed the presence of HDACs at the B-myc promoter.Conclusions:HDAC activities are essential for liver regeneration.Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest,thereby causing an anti-proliferative effect on liver regeneration.展开更多
The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented,but little research has been performed on rodent animals,e.g.,mice.In this study,we report osteoinduction ...The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented,but little research has been performed on rodent animals,e.g.,mice.In this study,we report osteoinduction in a mouse model.Thirty mice were divided into two groups.BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle,respectively.Five mice in each group were killed at 15,30,and 45 d after surgery.Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining,immunohistochemistry (IHC) staining,and Alizarin Red S staining to check bone formation in the biomaterials.Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups.Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation;the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%,respectively.However,we did not see any bone tissue in Sample B until 45 d after implantation.Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2),collagen type I,and osteopontin were detected by IHC staining in Sample A 30 d after implantation.In addition,the newly-formed bone was also confirmed by Alizarin Red S staining.Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available,our results may contribute to further mechanism research.展开更多
基金Project (Nos. 30971118 and 31000601) supported by the National Natural Science Foundation of China
文摘Background and objective:Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors.A variety of genetic factors have been reported,whereas few investigations have focused on epigenetic regulation during liver regeneration.In the present study,valproic acid(VPA),a histone deacetylase(HDAC) inhibitor,was used to investigate the effect of HDAC on liver regeneration.Methods:VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration.The mice were sacrificed,and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment.DNA synthesis was detected via a BrdU assay,and cell proliferation was tested using Ki-67.The expressions of cyclin D1,cyclin E,cyclin dependent kinase 2(CDK2),and CDK4 were detected by Western blot analysis.Chromatin immunoprecipitation(ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot.Results:Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased,and the peak of BrdU was delayed in the VPA-administered mice.Consistently,cyclin D1 expression was also delayed.We identified B-myc as a target gene of HDACs by complementary DNA(cDNA) microarray.The expression of B-myc increased in the VPA-administered mice after hepatectomy(PH).The ChIP assay confirmed the presence of HDACs at the B-myc promoter.Conclusions:HDAC activities are essential for liver regeneration.Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest,thereby causing an anti-proliferative effect on liver regeneration.
基金Project (No. 2005CB623901) supported by the National Basic Research Program (973) of China
文摘The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented,but little research has been performed on rodent animals,e.g.,mice.In this study,we report osteoinduction in a mouse model.Thirty mice were divided into two groups.BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle,respectively.Five mice in each group were killed at 15,30,and 45 d after surgery.Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining,immunohistochemistry (IHC) staining,and Alizarin Red S staining to check bone formation in the biomaterials.Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups.Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation;the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%,respectively.However,we did not see any bone tissue in Sample B until 45 d after implantation.Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2),collagen type I,and osteopontin were detected by IHC staining in Sample A 30 d after implantation.In addition,the newly-formed bone was also confirmed by Alizarin Red S staining.Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available,our results may contribute to further mechanism research.
