Inhibited Wnt Signaling Causes Age-Dependent Abnormalities in the Bone Matrix Mineralization in the Apert Syndrome FGFR2S252W/+ Mice
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{"title"=>"Inhibited Wnt signaling causes age-dependent abnormalities in the bone matrix mineralization in the apert syndrome FGFR2S252W/+ mice", "type"=>"journal", "authors"=>[{"first_name"=>"Li", "last_name"=>"Zhang", "scopus_author_id"=>"37062367200"}, {"first_name"=>"Peng", "last_name"=>"Chen", "scopus_author_id"=>"55791667700"}, {"first_name"=>"Lin", "last_name"=>"Chen", "scopus_author_id"=>"55739204000"}, {"first_name"=>"Tujun", "last_name"=>"Weng", "scopus_author_id"=>"22936061800"}, {"first_name"=>"Shichang", "last_name"=>"Zhang", "scopus_author_id"=>"55713485600"}, {"first_name"=>"Xia", "last_name"=>"Zhou", "scopus_author_id"=>"55622047700"}, {"first_name"=>"Bo", "last_name"=>"Zhang", "scopus_author_id"=>"56898214300"}, {"first_name"=>"Luchuan", "last_name"=>"Liu", "scopus_author_id"=>"23390004400"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"602339234", "doi"=>"10.1371/journal.pone.0112716", "sgr"=>"84923309971", "scopus"=>"2-s2.0-84923309971", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"25693202"}, "id"=>"fffd0f1d-1c26-3521-aeaa-b22253026493", "abstract"=>"Apert syndrome {(AS)} is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in internal organs. Approximately 70% of {AS} cases are caused by a single mutation, {S252W,} in fibroblast growth factor receptor 2 {(FGFR2).} Two groups have generated {FGFR2} knock-in mice {Fgfr2S252W/+} that exhibit features of {AS.} During the present study of {AS} using the {Fgfr2S252W/+} mouse model, an age-related phenotype of bone homeostasis was discovered. The long bone mass was lower in 2 month old mutant mice than in age-matched controls but higher in 5 month old mutant mice. This unusual phenotype suggested that bone marrow-derived mesenchymal stem cells {(BMSCs),} which are vital to maintain bone homeostasis, might be involved. {BMSCs} were isolated from {Fgfr2S252W/+} mice and found that {S252W} mutation could impair osteogenic differentiation {BMSCs} but enhance mineralization of more mature osteoblasts. A microarray analysis revealed that Wnt pathway inhibitors {SRFP1/2/4} were up-regulated in mutant {BMSCs.} This work provides evidence to show that the {Wnt/β-catenin} pathway is inhibited in both mutant {BMSCs} and osteoblasts, and differentiation defects of these cells can be ameliorated by Wnt3a treatment. The present study suggested that the bone abnormalities caused by deregulation of Wnt pathway may underlie the symptoms of {AS.}", "link"=>"http://www.mendeley.com/research/inhibited-wnt-signaling-causes-agedependent-abnormalities-bone-matrix-mineralization-apert-syndrome", "reader_count"=>8, "reader_count_by_academic_status"=>{"Librarian"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Librarian"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>2, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Denmark"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1910727"], "description"=>"<p>(A) There was no remarkable difference in total serum Ca or phosphate between wild-type and mutant mice at 2 months or at 5 months. (<i>n</i> = 6). (B) The serum levels of PINP as measured by ELISA were significantly lower in mutant mice at 2 months than in wild-type mice at 2 months. (C) These levels were significantly higher in mutant mice at 5 months than in wild-type mice at 5 months (<i>n</i> = 6). Graphs show mean value ±SD (Student's <i>t</i>-test, **<i>P</i><0.01).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312224, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g003", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_biochemistry_and_serum_level_of_PINP_of_wild_type_and_Fgfr2_S252W_mice_at_2_months_and_5_months_/1312224", "title"=>"Serum biochemistry and serum level of PINP of wild-type and <i>Fgfr2</i><sup>S252W/+</sup>mice at 2 months and 5 months.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910730"], "description"=>"<p>(A) CCK-8 assay showed that <i>Fgfr2</i><sup>S252W/+</sup> BMSCs proliferated more slowly than wild-type BMSCs. As indicated by the absorbance values, 2 days after inoculation, there was little increase in cell number of wild-type BMSCs; on day 4, there were significantly more cells; on day 6, the number of cells peaked and cell proliferation entered a stationary phase. The number of <i>Fgfr2</i><sup>S252W/+</sup> BMSCs did not change significantly during the first 4 days after inoculation. The first significant increase was observed on day 6 and the number of cells peaked on day 8. All growth phases of <i>Fgfr2</i><sup>S252W/+</sup> BMSCs lagged behind those of wild-type BMSCs. (B) After 21 days of adipogenic induction, lipid droplets were stained positive by oil red O in both <i>Fgfr2</i><sup>S252W/+</sup> BMSCs cultures and with wild-type BMSCs cultures, but <i>Fgfr2</i><sup>S252W/+</sup> BMSCs produced significantly fewer lipid droplets than wild-type BMSCs. (C) qRT-PCR detection of adipogenesis-related genes PPARγ and LPL. The results showed that adipogenic induction induced significantly less expression of PPARγ and LPL in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs than in wild-type BMSCs. Graphs show the mean value ±SD (Student's t-test, *** <i>P</i><0.001).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312227, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g004", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S252W_mutation_affected_both_proliferation_and_adipogenic_differentiation_of_BMSCs_/1312227", "title"=>"S252W mutation affected both proliferation and adipogenic differentiation of BMSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910734"], "description"=>"<p>(A) ALP staining showed less crystal violet-staining cells in cultured <i>Fgfr2</i><sup>S252W/+</sup> BMSCs than in wild-type BMSCs on days 4, 7, and 14. (B) There was significantly less ALP activity (normalized to the total protein content of the sample, 562 nm) in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs. (C) Alizarin red staining of the mineralized osteoblasts showed more mineralized nodules on day 21 after osteogenic differentiation in <i>Fgfr2</i><sup>S252W/+</sup> mice. (D) Bound alizarin red was dissolved with 5% SDS, 0.5 N HCl and measured at 415 nm to quantify the mineral content. Cultured <i>Fgfr2</i><sup>S252W/+</sup> BMSCs showed more mineral content. (E–H) Relative expression levels of osteogenic marker genes were measured using qRT–PCR. The levels of <i>oc, op</i>, Runx2 and osteorix mRNA expression in differentiated BMSCs were markedly lower in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs on days 4, 7, and 14, but markedly higher on day 21. The expression levels of Col1 mRNA in differentiated BMSCs were markedly lower in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs on day 4, but they were higher on day 7 and markedly higher on days 14 and 21. Graphs show mean value ±SD (Student's <i>t</i>-test, *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312231, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g005", "stats"=>{"downloads"=>0, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_S252W_mutation_on_the_osteogenic_differentiation_and_mineralization_of_BMSCs_/1312231", "title"=>"Effects of S252W mutation on the osteogenic differentiation and mineralization of BMSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910736"], "description"=>"<p>(A) Cluster analysis of a microarray data revealed that Wnt pathway antagonists SRRP1, SFRP2, and SFRP4 were up-regulated 3.8 fold, 2.5 fold, and 2.9 fold in mutant BMSCs, respectively (<i>n</i> = 3). (B) Relative expression levels of SFRP1, SFRP2, and SFRP4 measured by qRT–PCR. The expression levels of SFRP1, SFRP2, SFRP4 mRNA were markedly higher in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs. Graphs show mean value ±SD (Student's <i>t</i>-test, **<i>P</i><0.01, ***<i>P</i><0.001). The PCR results were consistent with microarray results. (C) Western blot analysis demonstrated that the levels of SFRP1, SFRP2, and SFRP4 were higher in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs cultured in standard medium. (D) <i>Fgfr2</i><sup>S252W/+</sup> BMSCs and wild-type BMSCs were kept in osteogenic differentiation medium. Cells were collected on the indicated days and then cytosol and nuclear levels of Wnt pathway effector β-catenin were examined by Western blot analysis. The results showed that β-catenin protein levels were lower in mutant cells than in wild type cells. (E) Relative expression levels of Wnt target genes <i>cyclinD1</i>, <i>lef1</i>, and <i>fzd4</i> were measured by qRT–PCR. The results showed that after 21 days of osteogenic induction, the mRNA levels of these genes were markedly decreased in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs. Graphs show mean value ±SD (Student's <i>t</i>-test, **<i>P</i><0.01, ***<i>P</i><0.001).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312233, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g006", "stats"=>{"downloads"=>13, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S252W_mutation_affected_Wnt_signaling_in_osteogenically_differentiating_BMSCs_/1312233", "title"=>"S252W mutation affected Wnt signaling in osteogenically differentiating BMSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910740"], "description"=>"<p>(A) CCK-8 proliferation assay showed <i>Fgfr2</i><sup>S252W/+</sup> BMSCs treated with Wnt3a to proliferate less than wild-type BMSCs treated with Wnt3a but more than untreated <i>Fgfr2</i><sup>S252W/+</sup>. (B) After 21 days of adipogenic induction, expression of adipogenesis-related genes PPARγ and LPL was examined using qRT -PCR. Results showed that expression levels of PPARγ and LPL in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs treated with Wnt3a were lower than in wild-type+Wnt3a BMSCs but significantly higher than in untreated <i>Fgfr2</i><sup>S252W/+</sup> BMSCs. (C) ALP staining showed more crystal violet-staining cells in cultured <i>Fgfr2</i><sup>S252W/+</sup> treated with Wnt3a BMSCs than in untreated <i>Fgfr2</i><sup>S252W/+</sup> BMSCs on days 7 and 14. (D) ALP activity (normalized to the total protein content of the sample, 562 nm) was significantly higher in <i>Fgfr2</i><sup>S252W/+</sup> treated with Wnt3a BMSCs than in untreated cells. (E) After 21 days of osteogenic differentiation, Alizarin red staining of the mineralized osteoblasts showed that wild-type BMSCs treated with Wnt3a had the fewest mineralized nodules, followed by <i>Fgfr2</i><sup>S252W/+</sup> treated with Wnt3a, and untreated <i>Fgfr2</i><sup>S252W/+</sup> BMSCs had the most nodules. (F) Cultured wild-type BMSCs treated with Wnt3a showed the least mineral content, followed by <i>Fgfr2</i><sup>S252W/+</sup> BMSCs treated with Wnt3a, and untreated <i>Fgfr2</i><sup>S252W/+</sup> BMSCs had the highest mineral content. (G) Relative expression levels of osteogenic marker genes were measured using qRT–PCR. The expression levels of <i>oc</i>, and Runx2 mRNA were markedly higher in differentiated <i>Fgfr2</i><sup>S252W/+</sup> treated with Wnt3a BMSCs than in untreated <i>Fgfr2</i><sup>S252W/+</sup> BMSCs on days 7 and 14, but markedly lower on day 21. The expression levels of Col1 were markedly higher in <i>Fgfr2</i><sup>S252W/+</sup> BMSCs treated with Wnt3a than in untreated <i>Fgfr2</i><sup>S252W/+</sup> BMSCs on days 7, but lower on day 14, 21. Graphs show mean value ±SD (Student's <i>t</i>-test, *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312237, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g007", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Activated_FGFR2_and_the_proliferation_adipogenic_differentiation_osteogenic_differentiation_and_mineralization_of_BMSCs_/1312237", "title"=>"Activated FGFR2 and the proliferation, adipogenic differentiation, osteogenic differentiation, and mineralization of BMSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910741"], "description"=>"<p>Primer with their sequence, length of amplification (bp) used for qRT-PCR in this study.</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312238, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primer_with_their_sequence_length_of_amplification_bp_used_for_qRT_PCR_in_this_study_/1312238", "title"=>"Primer with their sequence, length of amplification (bp) used for qRT-PCR in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910743", "https://ndownloader.figshare.com/files/1910744"], "description"=>"<div><p>Apert syndrome (AS) is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in internal organs. Approximately 70% of AS cases are caused by a single mutation, S252W, in fibroblast growth factor receptor 2 (FGFR2). Two groups have generated FGFR2 knock-in mice <i>Fgfr2</i><sup>S252W/+</sup> that exhibit features of AS. During the present study of AS using the <i>Fgfr2</i><sup>S252W/+</sup> mouse model, an age-related phenotype of bone homeostasis was discovered. The long bone mass was lower in 2 month old mutant mice than in age-matched controls but higher in 5 month old mutant mice. This unusual phenotype suggested that bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to maintain bone homeostasis, might be involved. BMSCs were isolated from <i>Fgfr2</i><sup>S252W/+</sup> mice and found that S252W mutation could impair osteogenic differentiation BMSCs but enhance mineralization of more mature osteoblasts. A microarray analysis revealed that Wnt pathway inhibitors SRFP1/2/4 were up-regulated in mutant BMSCs. This work provides evidence to show that the Wnt/β-catenin pathway is inhibited in both mutant BMSCs and osteoblasts, and differentiation defects of these cells can be ameliorated by Wnt3a treatment. The present study suggested that the bone abnormalities caused by deregulation of Wnt pathway may underlie the symptoms of AS.</p></div>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312240, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0112716.s001", "https://dx.doi.org/10.1371/journal.pone.0112716.s002"], "stats"=>{"downloads"=>13, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Inhibited_Wnt_Signaling_Causes_Age_Dependent_Abnormalities_in_the_Bone_Matrix_Mineralization_in_the_Apert_Syndrome_FGFR2_S252W_Mice/1312240", "title"=>"Inhibited Wnt Signaling Causes Age-Dependent Abnormalities in the Bone Matrix Mineralization in the Apert Syndrome FGFR2<sup>S252W/+</sup> Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910720"], "description"=>"<p>Quantitative micro-CT analyses of distal femoral metaphysic and middle shaft from wild-type and <i>Fgfr2</i><sup>S252W/+</sup> at 2 months and 5 months. (A and C) Three-dimensional images showed reduced trabecular and cortical bone at 2 months, but (B and D) there was more trabecular and cortical bone in mutant mice at 5 months. (E–G, J–M) Quantification of the structural parameters of the femoral metaphysis revealed that Tb.N, Tb.Th, Ct.Th, and Tb.BV/TV, Ct.BV/TV, Tb.BMD, and Ct.BMD were lower than in control mice, Tb.Sp and Tb.SMI were increased at 2 months in mutant mice relative to wild-type mice (<i>n</i> = 6)( H and I). (M) Although Ct.BMD levels were less at 5 months in mutant mice than in wild-type mice, Tb.N, Tb.Th, Ct.Th, and Tb.BV/TV, Ct.BV/TV, Tb.BMD levels were higher in mutant mice(E–G and J–L). (H and I) Tb.Sp and Tb.SMI were significantly less pronounced at 5 months in mutant mice than in wild-type mice (<i>n</i> = 6). Graphs show mean value ±SD (Student's <i>t</i>-test, *<i>P</i><0.05, **<i>P</i><0.01).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312217, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bone_abnormalities_in_Fgfr2_S252W_mice_/1312217", "title"=>"Bone abnormalities in <i>Fgfr2</i><sup>S252W/+</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1910725"], "description"=>"<p>(A and B) Von Kossa staining of undecalcified tibiae revealed that the proximal tibiae of <i>Fgfr2</i><sup>S252W/+</sup> mice had sparser trabecular bone than wild-type mice at 2 months, but they had longer and denser trabecular bone than wild-type mice at 5 months (magnification, ×40). (C and D) Histomorphometric measurements of tibiae. The tibiae from <i>Fgfr2</i><sup>S252W/+</sup> mice had significantly less Tb.BV/TV and more Tb.Sp at 2 months, but they had more Tb.BV/TV and less Tb.Sp at 5 months (n = 6). (E and F) H&E staining of tibiae showed the morphology of metaphyseal osteoblasts in the proximal tibia. Note that there were fewer osteoblasts lining trabecular bone in the <i>Fgfr2</i><sup>S252W/+</sup> mice at 2 months but they were more plump and cuboidal at 5 months (red arrows; magnification, ×400). (G and H) Von Kossa staining showed that osteoids laid down in the trabecular bone in <i>Fgfr2</i><sup>S252W/+</sup> mice were thinner than those of wild-type mice at 2 months old, but thicker than those of wild-type mice at 5 months (white arrows; magnification, ×400). Graphs show mean value ±SD (Student's <i>t</i>-test, *<i>P</i><0.05).</p>", "links"=>[], "tags"=>["osteogenic differentiation BMSCs", "Apert Syndrome FGFR 2S Mice Apert syndrome", "S 252W mutation", "osteoblast", "Wnt 3a treatment", "Fibroblast growth factor receptor 2", "Fgfr 2S mouse model", "Bone Matrix Mineralization", "bone homeostasis", "Fgfr 2S mice", "phenotype", "pathway", "SRFP", "as", "abnormality"], "article_id"=>1312222, "categories"=>["Biological Sciences"], "users"=>["Li Zhang", "Peng Chen", "Lin Chen", "Tujun Weng", "Shichang Zhang", "Xia Zhou", "Bo Zhang", "Luchuan Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112716.g002", "stats"=>{"downloads"=>0, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histochemical_analysis_of_decalcified_and_undecalcified_tibiae_from_2_and_5_month_old_mutant_and_wild_type_mice_/1312222", "title"=>"Histochemical analysis of decalcified and undecalcified tibiae from 2- and 5-month-old mutant and wild-type mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-18 03:31:53"}

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  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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