Arctigenin Inhibits Osteoclast Differentiation and Function by Suppressing Both Calcineurin-Dependent and Osteoblastic Cell-Dependent NFATc1 Pathways
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways", "type"=>"journal", "authors"=>[{"first_name"=>"Teruhito", "last_name"=>"Yamashita", "scopus_author_id"=>"7404186135"}, {"first_name"=>"Shunsuke", "last_name"=>"Uehara", "scopus_author_id"=>"7201895011"}, {"first_name"=>"Nobuyuki", "last_name"=>"Udagawa", "scopus_author_id"=>"56210408000"}, {"first_name"=>"Feng", "last_name"=>"Li", "scopus_author_id"=>"56428126300"}, {"first_name"=>"Shigetoshi", "last_name"=>"Kadota", "scopus_author_id"=>"35460007900"}, {"first_name"=>"Hiroyasu", "last_name"=>"Esumi", "scopus_author_id"=>"56526470300"}, {"first_name"=>"Yasuhiro", "last_name"=>"Kobayashi", "scopus_author_id"=>"36078955200"}, {"first_name"=>"Naoyuki", "last_name"=>"Takahashi", "scopus_author_id"=>"7403939332"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"84898464531", "doi"=>"10.1371/journal.pone.0085878", "scopus"=>"2-s2.0-84898464531", "pmid"=>"24465763", "pui"=>"372817887"}, "id"=>"ba5488e7-f29e-314c-b30e-4e960481ae24", "abstract"=>"Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit-forming activity of osteoclast-like cells cultured on dentin slices. These results suggest that arctigenin induces a dominant negative species of NFATc1, which inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.", "link"=>"http://www.mendeley.com/research/arctigenin-inhibits-osteoclast-differentiation-function-suppressing-both-calcineurindependent-osteob", "reader_count"=>16, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>6, "Chemical Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"Japan"=>1, "Switzerland"=>1}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84898464531"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84898464531?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84898464531&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84898464531&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84898464531", "dc:identifier"=>"SCOPUS_ID:84898464531", "eid"=>"2-s2.0-84898464531", "dc:title"=>"Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways", "dc:creator"=>"Yamashita T.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"9", "prism:issueIdentifier"=>"1", "prism:pageRange"=>nil, "prism:coverDate"=>"2014-01-17", "prism:coverDisplayDate"=>"17 January 2014", "prism:doi"=>"10.1371/journal.pone.0085878", "citedby-count"=>"6", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Matsumoto Dental University", "affiliation-city"=>"Shiojiri", "affiliation-country"=>"Japan"}], "pubmed-id"=>"24465763", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e85878", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0085878", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"55", "xml_views"=>"16", "html_views"=>"286"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"197"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"23", "xml_views"=>"2", "html_views"=>"162"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"47", "xml_views"=>"4", "html_views"=>"168"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"32", "xml_views"=>"1", "html_views"=>"205"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"184"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"149"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"2", "html_views"=>"51"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"64"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"67"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"17", "xml_views"=>"2", "html_views"=>"62"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"53"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"44"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"41"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"25", "xml_views"=>"1", "html_views"=>"50"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"15"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"74"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"41"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"3", "html_views"=>"10"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"7"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"1"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1350538"], "description"=>"<p>(A) Osteoclast-like cell formation in BMM cultures. BMMs were retrovirally transduced with constitutively active (ca)-NFATc1, wild-type (wt)-NFATc1, or control GFP genes, and cultured for 2 days in the presence of M-CSF. Cells were further cultured in the presence of RANKL and M-CSF together with or without 1 µM arctigenin or 1 µg/mL CsA. After cultivation for 3 days, cells were fixed and stained for TRAP. TRAP-positive multinucleated cells containing more than three nuclei were counted as osteoclast-like cells. The results were expressed as means +/− SD (n = 4). *, p<0.05. **, p<0.01. Bar = 50 µm. (B) Subcellular distribution of NFATc1. Nuclear and cytosol fractions were prepared from BMMs transfected with or without ca-NFATc1 and wt-NFATc1 and analyzed by Western blotting with the anti-NFATc1 antibody.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "arctigenin", "osteoclast-like", "induced", "forced"], "article_id"=>903456, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085878.g004", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_arctigenin_on_osteoclast_like_cell_formation_induced_by_the_forced_expression_of_NFATc1_/903456", "title"=>"Effect of arctigenin on osteoclast-like cell formation induced by the forced expression of NFATc1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 03:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1350536"], "description"=>"<p>(A) Effects of arctigenin and CsA on the nuclear translocation of NFATc1 and NF-κB in osteoclast-like cells. Purified osteoclast-like cells were cultured for 16 h in the absence of RANKL. Osteoclast-like cells were then pre-treated for 20 min with or without 1 µM arctigenin or 1 µg/mL CsA, and then further incubated for 20 min with or without RANKL. Nuclear fractions were analyzed by Western blotting with the antibodies indicated. (B) Immunohistochemical detection of NFATc1 in osteoclast-like cells. Purified osteoclast-like cells were cultured on glass plates for 16 h in the absence of RANKL. Cells were then treated for 20 min with or without 1 µM arctigenin or 100 ng/mL RANKL. Cells were fixed and stained for NFATc1 (green). Nuclei were counterstained with propidium iodide (PI, red). Bar = 50 µm. (C) Effects of arctigenin and CsA on NFAT reporter activity. BMMs were transfected with the NFAT-luciferase construct. Forty-eight hours later, cells were incubated for an additional 24 h with or without ionomycin and PMA. Some cultures were treated with 1 µM arctigenin or 1 µg/mL CsA. The fluorescence of the lysates was measured by a luminometer. The results were expressed as means +/− SD (n = 3). *, p<0.05. (D) ChIP assay on the <i>Oscar</i> promoter. BMMs were cultured for 2 days in the presence of RANKL and M-CSF. Cells were then treated for 1 h with or without 1 µM arctigenin. Chromatin complexes were immunoprecipitated with the anti-NFATc1 antibody or control IgG. Chromatin DNA fragments were subjected to PCR for the <i>Oscar</i> promoter. (E) Western blotting of NFATc1 in osteoclast-like cells. Purified osteoclast-like cells were treated for 10 min with or without 1 µM arctigenin or 1 µg/mL CsA. Cell lysates were then collected. Half of the lysates were treated for 30 min with calf intestine alkaline phosphatase (CIAP). Samples were analyzed by Western blotting with the anti-NFATc1 antibody.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "arctigenin", "translocation", "activation"], "article_id"=>903454, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085878.g003", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_arctigenin_on_the_nuclear_translocation_and_activation_of_NFATc1_/903454", "title"=>"Effects of arctigenin on the nuclear translocation and activation of NFATc1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 03:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1350532"], "description"=>"<p>(A) Chemical structures of arctigenin, arctiin, and secoisolariciresinol. (B) Effects of lignan-derived compounds on osteoclast-like cell formation in BMM cultures. BMMs were cultured in 96-well culture plates in the presence of RANKL and M-CSF together with increasing concentrations of the lignan-derived compounds. After cultivation for 3 days, cells were stained for TRAP. TRAP-positive cells appeared as dark red cells. TRAP-positive multinucleated cells containing more than three nuclei were counted as osteoclast-like cells. (C) Effects of arctigenin on the proliferation of BMMs. BMMs were cultured in the presence of M-CSF together with increasing concentrations of arctigenin. Cell proliferation was evaluated on days 0, 1, 2, and 3 using an Alamar Blue assay. The results were expressed as means +/− SD (n = 3). *, p<0.05.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "arctigenin", "osteoclast-like", "proliferation", "bmm"], "article_id"=>903450, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085878.g001", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_arctigenin_on_osteoclast_like_cell_formation_and_cell_proliferation_in_BMM_cultures_/903450", "title"=>"Effects of arctigenin on osteoclast-like cell formation and cell proliferation in BMM cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 03:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1350546"], "description"=>"<p>(A) Effects of arctigenin on the pit-forming activity of osteoclast-like cells cultured on dentin slices. Osteoclast-like cell preparations were cultured on dentin slices in the presence or absence of 1 µM arctigenin. After cultivation for 48 h, cells on the slices were fixed and stained for TRAP. TRAP-positive cells were counted as osteoclast-like cells. Cells were then removed from dentin slices, and slices were stained with Mayer's hematoxylin to visualize resorption pits. Resorption pit areas were measured using ImageJ software. The results were expressed as means +/− SD (n = 6). *, p<0.01. Bar = 50 µm. (B) Effect of arctigenin on actin ring formation by osteoclast-like cells. Osteoclast-like cell preparations were cultured on dentin slices in the presence or absence of 1 µM arctigenin. After cultivation for 24 h, cells on the slices were fixed and stained with Rhodamine-phalloidin. Bar = 50 µm. (C) A hypothetical model for the action of arctigenin on the differentiation and function of osteoclasts. Arctigenin inhibited RANKL-induced osteoclast-like cell formation in BMM cultures, in which the Ca<sup>2+</sup>/calcineurin-dependent NFATc1 pathway was activated. Arctigenin also inhibited osteoclast-like cell formation in co-cultures with osteoblastic cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The pit-forming activity of osteoclast-like cells was also inhibited by arctigenin. Arctigenin induced a lower molecular weight species of NFATc1, which may act as the dominant negative inhibitor of NFATc1.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "arctigenin", "osteoclast-like"], "article_id"=>903464, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085878.g006", "stats"=>{"downloads"=>3, "page_views"=>57, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_arctigenin_on_osteoclast_like_cell_function_/903464", "title"=>"Effect of arctigenin on osteoclast-like cell function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 03:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1350541"], "description"=>"<p>(A) Effects of arctigenin and CsA on osteoclast-like cell formation in the co-culture. Osteoblastic cells and bone marrow cells were co-cultured in the presence of 1α,25(OH)<sub>2</sub>D<sub>3</sub> together with or without 1 µM arctigenin or 1 µg/mL CsA. After cultivation for 6 days, cells were fixed and stained for TRAP. TRAP-positive multinucleated cells containing more than three nuclei were counted as osteoclast-like cells. Bar = 50 µm. (B) Effects of arctigenin on RANKL and OPG expression in osteoblastic cells. Osteoblastic cells were cultured for 24 h in the presence or absence of 10 nM 1α,25(OH)<sub>2</sub>D<sub>3</sub> together with or without 1 µM arctigenin. The expression of <i>Rankl</i> and <i>Opg</i> mRNAs was analyzed by quantitative RT-PCR. The expression level was normalized to <i>Gapdh</i> and expressed relative to the vehicle control. (C) Alkaline phosphatase staining of osteoblastic cell cultures. Osteoblastic cells were cultured for 6 days in the presence or absence of 1 µM arctigenin. Cells were then fixed and stained for alkaline phosphatase. Alkaline phosphatase-positive cells appeared as blue cells. Bar = 50 µm. (D) Effects of arctigenin on the proliferation of osteoblastic cells. Osteoblastic cells were cultured with increasing concentrations of arctigenin. Cell proliferation was evaluated on days 0, 1, and 2 using an Alamar Blue assay. The results were expressed as means +/− SD (n = 3). p<0.05.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "arctigenin", "osteoclast-like", "co-culture", "osteoblastic"], "article_id"=>903459, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085878.g005", "stats"=>{"downloads"=>3, "page_views"=>58, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_arctigenin_on_osteoclast_like_cell_formation_in_the_co_culture_with_osteoblastic_cells_/903459", "title"=>"Effect of arctigenin on osteoclast-like cell formation in the co-culture with osteoblastic cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 03:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1350553", "https://ndownloader.figshare.com/files/1350554", "https://ndownloader.figshare.com/files/1350556", "https://ndownloader.figshare.com/files/1350557", "https://ndownloader.figshare.com/files/1350558", "https://ndownloader.figshare.com/files/1350559"], "description"=>"<div><p>Arctigenin, a lignan-derived compound, is a constituent of the seeds of <i>Arctium lappa</i>. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit-forming activity of osteoclast-like cells cultured on dentin slices. These results suggest that arctigenin induces a dominant negative species of NFATc1, which inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.</p></div>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "inhibits", "osteoclast", "differentiation", "suppressing", "calcineurin-dependent", "osteoblastic", "cell-dependent", "nfatc1"], "article_id"=>903470, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085878.s001", "https://dx.doi.org/10.1371/journal.pone.0085878.s002", "https://dx.doi.org/10.1371/journal.pone.0085878.s003", "https://dx.doi.org/10.1371/journal.pone.0085878.s004", "https://dx.doi.org/10.1371/journal.pone.0085878.s005", "https://dx.doi.org/10.1371/journal.pone.0085878.s006"], "stats"=>{"downloads"=>12, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Arctigenin_Inhibits_Osteoclast_Differentiation_and_Function_by_Suppressing_Both_Calcineurin_Dependent_and_Osteoblastic_Cell_Dependent_NFATc1_Pathways_/903470", "title"=>"Arctigenin Inhibits Osteoclast Differentiation and Function by Suppressing Both Calcineurin-Dependent and Osteoblastic Cell-Dependent NFATc1 Pathways", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-17 03:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1350534"], "description"=>"<p>(A) Effects of arctigenin on the expression of osteoclast-related genes. BMMs were cultured in the presence of RANKL and M-CSF together with or without 1 µM arctigenin. After cultivation for the indicated periods, the expression of <i>Acp5</i>, <i>Ctsk</i>, <i>Oscar</i>, <i>Nfatc1</i>, and <i>c-Fos</i> mRNAs was analyzed by quantitative RT-PCR. Expression levels were normalized to <i>Gapdh</i> and expressed relative to day 0. Statistical analysis was performed between the control and arctigenin-treated values at indicated time points. (B) Effects of arctigenin on RANKL-induced signals in BMMs. BMMs were pretreated for 10 min with 1 µM arctigenin and further treated with RANKL. Whole cell lysates were harvested and analyzed by Western blotting with the indicated antibodies. (C) Effects of arctigenin, CsA, and SB203580 on osteoclast-like cell formation in BMM cultures. BMMs were cultured for 3 days in the presence of RANKL and M-CSF. BMM cultures were also treated with 1 µM arctigenin, 1 µg/mL CsA, or 1 µM SB203580 during days 0 – 3 and days 1 – 3. Cells were then fixed and stained for TRAP. TRAP-positive multinucleated cells containing more than three nuclei were counted as osteoclast-like cells. The results were expressed as means +/− SD (n = 3). *, p<0.05.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Musculoskeletal system", "bone", "Biochemistry", "metabolism", "Bone and mineral metabolism", "Computational biology", "Molecular genetics", "gene expression", "developmental biology", "Cell differentiation", "genetics", "Molecular cell biology", "Cellular types", "Bone marrow cells", "Signal transduction", "Signaling in cellular processes", "rheumatology", "arctigenin", "rankl-induced"], "article_id"=>903452, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Teruhito Yamashita", "Shunsuke Uehara", "Nobuyuki Udagawa", "Feng Li", "Shigetoshi Kadota", "Hiroyasu Esumi", "Yasuhiro Kobayashi", "Naoyuki Takahashi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085878.g002", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_arctigenin_on_RANKL_induced_signaling_in_BMMs_/903452", "title"=>"Effects of arctigenin on RANKL-induced signaling in BMMs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-17 03:24:57"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"63", "full-text"=>"57", "pdf"=>"45", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"42", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"44", "full-text"=>"61", "pdf"=>"27", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"31", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"25", "full-text"=>"14", "pdf"=>"10", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"25", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"30", "full-text"=>"21", "pdf"=>"14", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"19", "full-text"=>"19", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"23", "full-text"=>"20", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"26", "full-text"=>"24", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"23", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"26", "full-text"=>"16", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"27", "full-text"=>"26", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"26", "full-text"=>"17", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"2", "cited-by"=>"1", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"24", "full-text"=>"24", "pdf"=>"8", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"34", "full-text"=>"23", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"29", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"46", "full-text"=>"33", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"15", "full-text"=>"12", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"23", "full-text"=>"16", "pdf"=>"5", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"27", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"21", "full-text"=>"18", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"17", "full-text"=>"30", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"21", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"35", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"15", "cited-by"=>"1", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[267]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[266]}]}
Loading … Spinner
There are currently no alerts