The Wnt/β-Catenin Pathway Interacts Differentially with PTHrP Signaling to Control Chondrocyte Hypertrophy and Final Maturation
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{"title"=>"The Wnt/β-catenin pathway interacts differentially with PTHrP signaling to control chondrocyte hypertrophy and final maturation", "type"=>"journal", "authors"=>[{"first_name"=>"Xizhi", "last_name"=>"Guo", "scopus_author_id"=>"8215748800"}, {"first_name"=>"Kinglun Kingston", "last_name"=>"Mak", "scopus_author_id"=>"24171782800"}, {"first_name"=>"Makoto M.", "last_name"=>"Taketo", "scopus_author_id"=>"7004878460"}, {"first_name"=>"Yingzi", "last_name"=>"Yang", "scopus_author_id"=>"7409389935"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"19557172", "sgr"=>"67649484495", "doi"=>"10.1371/journal.pone.0006067", "scopus"=>"2-s2.0-67649484495", "pui"=>"354811574", "isbn"=>"1932-6203 (Electronic)", "issn"=>"19326203"}, "id"=>"9e04407e-9ff2-3ba8-b44b-c4eeb0059dbe", "abstract"=>"Sequential proliferation, hypertrophy and maturation of chondrocytes are required for proper endochondral bone development and tightly regulated by cell signaling. The canonical Wnt signaling pathway acts through beta-catenin to promote chondrocyte hypertrophy whereas PTHrP signaling inhibits it by holding chondrocytes in proliferating states. Here we show by genetic approaches that chondrocyte hypertrophy and final maturation are two distinct developmental processes that are differentially regulated by Wnt/beta-catenin and PTHrP signaling. Wnt/beta-catenin signaling regulates initiation of chondrocyte hypertrophy by inhibiting PTHrP signaling activity, but it does not regulate PTHrP expression. In addition, Wnt/beta-catenin signaling regulates chondrocyte hypertrophy in a non-cell autonomous manner and Gdf5/Bmp signaling may be one of the downstream pathways. Furthermore, Wnt/beta-catenin signaling also controls final maturation of hypertrophic chondrocytes, but such regulation is PTHrP signaling-independent.", "link"=>"http://www.mendeley.com/research/wnt%CE%B2catenin-pathway-interacts-differentially-pthrp-signaling-control-chondrocyte-hypertrophy-final-m", "reader_count"=>30, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Materials Science"=>1, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "South Africa"=>1}, "group_count"=>1}

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  • {"files"=>["https://ndownloader.figshare.com/files/893724"], "description"=>"<p>(A) Sections of developing humerus at 14.5 dpc were examined by in situ hybridization with <i>PTHrP</i> probes. Expression of <i>PTHrP</i> was reduced in periarticular chondrocytes in <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> single mutant embryos compared to that in wild type embryos. <i>PTHrP</i> expression was increased in the double mutant embryos compared to that in the <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> single mutant embryos. (B) Skeletal preparation of 16.5 dpc embryos. A forelimb of each embryo is shown in lower panel. Alizarin red stains the mineralized hypertrophic chondrocytes and bone. Alcian blue stains the unmineralized cartilage. Mineralization was accelerated in the <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> double mutant and the <i>PTHrP<sup>−/−</sup></i> single mutant. The bracket indicates the non-mineralized cartilage at the joint region. (C) Consecutive sections of the radius at 14.5 dpc were examined by in situ hybridization with probes of <i>Lef1</i> and <i>Tcf1</i>. <i>Lef1</i> and <i>Tcf1</i> expression were downregulated in both <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> single mutant and <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> double mutant embryos. (D) Consecutive sections of the developing humerus at 14.5 dpc were examined by Safranin O staining and in situ hybridization with the indicated riboprobes. Safranin O staining and expression of <i>Col2a1</i> marked nonhypertrophic chondrocytes. The nonhypertrophic domain (double headed arrow) was expanded in <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant embryos whereas it was shortened to the same degree in <i>PTHrP<sup>−/−</sup></i> single mutant and <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> double mutant embryos. <i>Col10a1</i> expression marked hypertrophic region, which was accelerated to the same level in <i>PTHrP<sup>−/−</sup></i> single mutant and <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> double mutant embryos.</p>", "links"=>[], "tags"=>["mutant"], "article_id"=>564186, "categories"=>["Developmental Biology", "Cell Biology", "Genetics"], "users"=>["Xizhi Guo", "Kinglun Kingston Mak", "Makoto M. Taketo", "Yingzi Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006067.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_PTHrP_and_946_catenin_mutant_skeletons_/564186", "title"=>"Analysis of <i>PTHrP</i> and <i>β-catenin</i> mutant skeletons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-26 01:09:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/894235"], "description"=>"<p>Tamoxifen was injected into pregnant females at 13.5 dpc. Embryos were harvested at 17.5 dpc and sections of the proximal tibia were analyzed by Safranin O staining, in situ hybridization with the indicated probes and immnohistochemistry. (A) Upregulated Wnt/β-catenin signaling was indicated by ectopic <i>Lef1</i> expression and loss of Safranin O staining and <i>Col2a1</i> expression (arrow). Pictures of higher magnification of the boxed area are shown as insets. <i>Col10a1</i> expression was not ectopically detected in chondrocytes that had lost <i>Col2a1</i> expression. (B) Increased p-Smad1/5/8 staining (red) was observed in chondrocyte patches of <i>Catnb<sup>ex3/+</sup>; Col2a1-CreER</i> mouse embryos. Such increase in p-Smad1/5/8 staining was in the area with increased β-catenin staining (green). But p-Smad1/5/8 and β-catenin staining did not colocalize in many chondrocytes. Some cells with increased p-Smad1/5/8 staining (arrows) did not show increased β-catenin staining. (C) Distinct genetic interactions between Wnt/β-catenin and PTHrP signaling in regulating chondrocyte hypertrophy and maturation. The sequential process of chondrocyte hypertrophy and maturation in developing wild type and indicated mutant long bone cartilage were shown in the diagram in the upper panel. Hypertrophic chondrocytes are enlarged and undergo final maturation before they are replaced by the trabecular bone. Initiation of chondrocyte hypertrophy and final maturation are two separate processes that are differentially regulated by Wnt/β-catenin and PTHrP signaling. Wnt/β-catenin signaling controls chondrocyte hypertrophy by inhibiting PTHrP signaling activity. However, Wnt/β-catenin signaling promoted final maturation of hypertrophic chondrocyte independently of PTHrP signaling.</p>", "links"=>[], "tags"=>["chondrocyte", "hypertrophy", "non-cell"], "article_id"=>564692, "categories"=>["Developmental Biology", "Cell Biology", "Genetics"], "users"=>["Xizhi Guo", "Kinglun Kingston Mak", "Makoto M. Taketo", "Yingzi Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006067.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_946_catenin_may_control_chondrocyte_hypertrophy_non_cell_autonomously_/564692", "title"=>"β-catenin may control chondrocyte hypertrophy non-cell autonomously.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-26 01:18:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/893902"], "description"=>"<p>(A) Skeletal preparation of 18.5 dpc embryos. Mineralization (stained by Alizarin red) in the <i>Catnb<sup>c/c</sup>; Smo<sup>c/c</sup>; Col2a1-Cre</i> double mutant embryo was more advanced than that in the <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant embryo, but less advanced than that in the <i>Smo<sup>c/c</sup>; Col2a1-Cre</i> mutant embryo. (B) Sections of the developing distal tibia at 15.5 dpc were examined by in situ hybridization with <i>PTHrP</i> probes. <i>PTHrP</i> expression was slightly reduced only in the periarticular chondrocytes in <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant embryos compared to that in wild type embryos. <i>Catnb<sup>c/c</sup>; Smo<sup>c/c</sup>; Col2a1-Cre</i> and <i>Smo<sup>c/c</sup>; Col2a1-Cre</i> embryos have similar expression of <i>PTHrP</i>. (C) Safranin O staining and <i>Col10a1</i> expression in the developing humerus at 15.5 dpc. Non-hypertrophic chondrocyte region (white line) was expanded in the <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant, but reduced in the <i>Smo<sup>c/c</sup>; Col2a1-Cre</i> mutant embryo, compared that in the wild type control. Chondrocyte hypertrophy in the <i>Catnb<sup>c/c</sup>; Smo<sup>c/c</sup>; Col2a1-Cre</i> double mutant embryo was delayed than that in the <i>Smo<sup>c/c</sup>; Col2a1-Cre</i> mutant embryo, but accelerated than that in the <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant embryo.</p>", "links"=>[], "tags"=>["chondrocyte", "hypertrophy", "mutant"], "article_id"=>564362, "categories"=>["Developmental Biology", "Cell Biology", "Genetics"], "users"=>["Xizhi Guo", "Kinglun Kingston Mak", "Makoto M. Taketo", "Yingzi Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006067.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_chondrocyte_hypertrophy_in_946_catenin_and_Smo_mutant_embryos_/564362", "title"=>"Analysis of chondrocyte hypertrophy in <i>β-catenin</i> and <i>Smo</i> mutant embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-26 01:12:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/442656", "https://ndownloader.figshare.com/files/442680", "https://ndownloader.figshare.com/files/442709", "https://ndownloader.figshare.com/files/442741"], "description"=>"<div><p>Sequential proliferation, hypertrophy and maturation of chondrocytes are required for proper endochondral bone development and tightly regulated by cell signaling. The canonical Wnt signaling pathway acts through β-catenin to promote chondrocyte hypertrophy whereas PTHrP signaling inhibits it by holding chondrocytes in proliferating states. Here we show by genetic approaches that chondrocyte hypertrophy and final maturation are two distinct developmental processes that are differentially regulated by Wnt/β-catenin and PTHrP signaling. Wnt/β-catenin signaling regulates initiation of chondrocyte hypertrophy by inhibiting PTHrP signaling activity, but it does not regulate <em>PTHrP</em> expression. In addition, Wnt/β-catenin signaling regulates chondrocyte hypertrophy in a non-cell autonomous manner and Gdf5/Bmp signaling may be one of the downstream pathways. Furthermore, Wnt/β-catenin signaling also controls final maturation of hypertrophic chondrocytes, but such regulation is PTHrP signaling-independent.</p></div>", "links"=>[], "tags"=>["pathway", "interacts", "differentially", "pthrp", "signaling", "chondrocyte", "hypertrophy", "maturation"], "article_id"=>147238, "categories"=>["Developmental Biology", "Cell Biology", "Genetics"], "users"=>["Xizhi Guo", "Kinglun Kingston Mak", "Makoto M. Taketo", "Yingzi Yang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0006067.s001", "https://dx.doi.org/10.1371/journal.pone.0006067.s002", "https://dx.doi.org/10.1371/journal.pone.0006067.s003", "https://dx.doi.org/10.1371/journal.pone.0006067.s004"], "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Wnt_Catenin_Pathway_Interacts_Differentially_with_PTHrP_Signaling_to_Control_Chondrocyte_Hypertrophy_and_Final_Maturation/147238", "title"=>"The Wnt/β-Catenin Pathway Interacts Differentially with PTHrP Signaling to Control Chondrocyte Hypertrophy and Final Maturation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-06-26 02:00:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/894068"], "description"=>"<p>Consecutive sections of the developing humerus at 14.5 dpc and 16.5 dpc were examined by Von Kossa staining and in situ hybridization with the indicated riboprobes. Mature hypertrophic chondrocytes were stained black by the Von Kossa method and expressed <i>Mmp13</i> and <i>Opn</i>. (A) Von Kossa staining and <i>Mmp13</i> and <i>Opn</i> expression were much reduced in both <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> and <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant embryos at 14.5 dpc. (B) <i>Ihh</i> and <i>Pthr1</i> were expressed in the less mature hypertrophic chondrocytes (double-headed arrow). This domain was expanded significantly only in the <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant embryos at 14.5 dpc. (C) At 16.5 dpc, chondrocyte final maturation in the <i>Catnb<sup>c/c</sup>; Col2a1-Cre</i> and <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant was similar to that of the wild type control and <i>PTHrP<sup>−/−</sup></i> mutant, respectively. (D) Expansion of <i>Ihh</i> and <i>Pthr1</i> expression domains (white line) were still observed in the <i>PTHrP<sup>−/−</sup>; Catnb<sup>c/c</sup>; Col2a1-Cre</i> mutant at 16.5 dpc. (E) Expression of <i>Mmp9</i> and <i>Vegf</i> in the developing humerus of the indicated genotypes at 14.5 dpc.</p>", "links"=>[], "tags"=>["chondrocyte", "maturation", "was", "regulated", "independently"], "article_id"=>564525, "categories"=>["Developmental Biology", "Cell Biology", "Genetics"], "users"=>["Xizhi Guo", "Kinglun Kingston Mak", "Makoto M. Taketo", "Yingzi Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006067.g003", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hypertrophic_chondrocyte_maturation_was_regulated_by_catenin_independently_of_PTHrP_/564525", "title"=>"Hypertrophic chondrocyte maturation was regulated by β-catenin independently of <i>PTHrP</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-06-26 01:15:25"}

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  • {"unique-ip"=>"12", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
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  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
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  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
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Relative Metric

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