The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"gro...The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the mo...Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.展开更多
文摘The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+1 种基金the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(RRR,TCH),the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH).
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.
