Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations
Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal integrity through coupled bone turnover. OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activa...
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| description | Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal integrity through coupled bone turnover. OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a specific subpopulation of defined osteoclast progenitor cells (dOCPs) with surface expression of B220(-)Gr1(-)CD11b(lo/-)CD115(+) (dOCP(lo/-)). In this study, we isolated dOCPs from male and female mice to determine sex-specific effects of MK2 signaling in osteoclastogenesis (OCgen). Male Mk2(-/-) mice display an increase in the dOCP(lo) cell population when compared to Mk2(+/+) mice, while female Mk2(-/-) and Mk2(+/+ )mice exhibit no difference. Defined OCPs from male and female Mk2(+/+) and Mk2(-/-) bone marrow were treated with macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote OCgen. RANKL treatment of dOCP(lo) cells stimulated p38 and MK2 phosphorylation. Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was critical for male dOCP(lo) OCgen, yet MK2 signaling regulated OCgen from female dOCP- and CD11b(hi) subpopulations as well. The functional gene, Ctsk, was attenuated in both male and female Mk2(-/-) dOCP(lo)-derived OCs. Conversely, MK2 signaling was only critical for gene expression of pre-OC fusion genes, Oc-stamp andTm7sf4, in male OCgen. Therefore, these data suggest there is a sexual dimorphism in MK2 signaling of OCP subpopulations. |
| doi_str_mv | 10.1371/journal.pone.0125387 |
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OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a specific subpopulation of defined osteoclast progenitor cells (dOCPs) with surface expression of B220(-)Gr1(-)CD11b(lo/-)CD115(+) (dOCP(lo/-)). In this study, we isolated dOCPs from male and female mice to determine sex-specific effects of MK2 signaling in osteoclastogenesis (OCgen). Male Mk2(-/-) mice display an increase in the dOCP(lo) cell population when compared to Mk2(+/+) mice, while female Mk2(-/-) and Mk2(+/+ )mice exhibit no difference. Defined OCPs from male and female Mk2(+/+) and Mk2(-/-) bone marrow were treated with macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote OCgen. RANKL treatment of dOCP(lo) cells stimulated p38 and MK2 phosphorylation. Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was critical for male dOCP(lo) OCgen, yet MK2 signaling regulated OCgen from female dOCP- and CD11b(hi) subpopulations as well. The functional gene, Ctsk, was attenuated in both male and female Mk2(-/-) dOCP(lo)-derived OCs. Conversely, MK2 signaling was only critical for gene expression of pre-OC fusion genes, Oc-stamp andTm7sf4, in male OCgen. Therefore, these data suggest there is a sexual dimorphism in MK2 signaling of OCP subpopulations.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0125387</identifier><identifier>PMID: 25946081</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acid phosphatase ; Acid phosphatase (tartrate-resistant) ; Acid Phosphatase - metabolism ; Acid resistance ; Animals ; Arthritis ; Biochemistry ; Biocompatibility ; Biological research ; Bone marrow ; Bone Marrow Cells ; Bone turnover ; Cathepsin K - genetics ; CD11b antigen ; Cell cycle ; Cell Differentiation ; Cells (biology) ; Cells, Cultured ; Cytokines ; Dimorphism (Biology) ; Disease ; Enzymatic activity ; Enzyme activity ; Female ; Females ; Gender differences ; Gene expression ; Gene fusion ; Health sciences ; Inflammation ; Intracellular Signaling Peptides and Proteins - metabolism ; Isoenzymes - metabolism ; Kinases ; Ligands (Biochemistry) ; Macrophage colony-stimulating factor ; Macrophages ; Male ; MAP kinase ; Medical research ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitogen-activated protein kinases ; NF-κB protein ; NFATC Transcription Factors - metabolism ; Oral hygiene ; Osteoclastogenesis ; Osteoclasts ; Osteoclasts (Biology) ; Osteoclasts - cytology ; Osteoclasts - metabolism ; Osteoprogenitor cells ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphorylation ; Physiological aspects ; Physiology ; Protein kinase ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; RANK Ligand - metabolism ; Rodents ; Sex Characteristics ; Sexual dimorphism ; Signal Transduction ; Signaling ; Stem Cells - cytology ; Stimulation ; Subpopulations ; Substrates ; Tartrate-Resistant Acid Phosphatase ; TRANCE protein ; Transcription factors ; Womens health</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0125387-e0125387</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Herbert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Herbert et al 2015 Herbert et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-8d5230489e3501ad9e3ae59dd3fb05c0a2e1419b6949a3c70a9a9d422a112a7b3</citedby><cites>FETCH-LOGICAL-c659t-8d5230489e3501ad9e3ae59dd3fb05c0a2e1419b6949a3c70a9a9d422a112a7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422514/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422514/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25946081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tintut, Yin</contributor><creatorcontrib>Herbert, Bethany A</creatorcontrib><creatorcontrib>Valerio, Michael S</creatorcontrib><creatorcontrib>Gaestel, Matthias</creatorcontrib><creatorcontrib>Kirkwood, Keith L</creatorcontrib><title>Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal integrity through coupled bone turnover. OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a specific subpopulation of defined osteoclast progenitor cells (dOCPs) with surface expression of B220(-)Gr1(-)CD11b(lo/-)CD115(+) (dOCP(lo/-)). In this study, we isolated dOCPs from male and female mice to determine sex-specific effects of MK2 signaling in osteoclastogenesis (OCgen). Male Mk2(-/-) mice display an increase in the dOCP(lo) cell population when compared to Mk2(+/+) mice, while female Mk2(-/-) and Mk2(+/+ )mice exhibit no difference. Defined OCPs from male and female Mk2(+/+) and Mk2(-/-) bone marrow were treated with macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote OCgen. RANKL treatment of dOCP(lo) cells stimulated p38 and MK2 phosphorylation. Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was critical for male dOCP(lo) OCgen, yet MK2 signaling regulated OCgen from female dOCP- and CD11b(hi) subpopulations as well. The functional gene, Ctsk, was attenuated in both male and female Mk2(-/-) dOCP(lo)-derived OCs. Conversely, MK2 signaling was only critical for gene expression of pre-OC fusion genes, Oc-stamp andTm7sf4, in male OCgen. Therefore, these data suggest there is a sexual dimorphism in MK2 signaling of OCP subpopulations.</description><subject>Acid phosphatase</subject><subject>Acid phosphatase (tartrate-resistant)</subject><subject>Acid Phosphatase - metabolism</subject><subject>Acid resistance</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Biochemistry</subject><subject>Biocompatibility</subject><subject>Biological research</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells</subject><subject>Bone turnover</subject><subject>Cathepsin K - genetics</subject><subject>CD11b antigen</subject><subject>Cell cycle</subject><subject>Cell Differentiation</subject><subject>Cells (biology)</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Dimorphism (Biology)</subject><subject>Disease</subject><subject>Enzymatic activity</subject><subject>Enzyme activity</subject><subject>Female</subject><subject>Females</subject><subject>Gender differences</subject><subject>Gene expression</subject><subject>Gene fusion</subject><subject>Health sciences</subject><subject>Inflammation</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Isoenzymes - metabolism</subject><subject>Kinases</subject><subject>Ligands (Biochemistry)</subject><subject>Macrophage colony-stimulating factor</subject><subject>Macrophages</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mitogen-activated protein kinases</subject><subject>NF-κB protein</subject><subject>NFATC Transcription Factors - metabolism</subject><subject>Oral hygiene</subject><subject>Osteoclastogenesis</subject><subject>Osteoclasts</subject><subject>Osteoclasts (Biology)</subject><subject>Osteoclasts - cytology</subject><subject>Osteoclasts - metabolism</subject><subject>Osteoprogenitor cells</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Protein kinase</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>RANK Ligand - metabolism</subject><subject>Rodents</subject><subject>Sex Characteristics</subject><subject>Sexual dimorphism</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Stem Cells - cytology</subject><subject>Stimulation</subject><subject>Subpopulations</subject><subject>Substrates</subject><subject>Tartrate-Resistant Acid Phosphatase</subject><subject>TRANCE protein</subject><subject>Transcription factors</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUttu1DAQjRCIloU_QBCJl_KQxbdc_IIUldtqt7Rq4dly7MnWqyQOdlLBZ_DHOGxauqi2pbHG5xzPjE4UvcRoiWmO3-3s6DrZLHvbwRJhktIifxQdY05JkhFEH9-7H0XPvN8hFDBZ9jQ6IilnGSrwcfT7Cn6Osok_mNa6_tr4NjZdfFZerJNSDeZGDqDjC2cHCOm16aSHhMQnZ2vyNr6E7djIwdgutnV8WX5db5JVp0cVKOd-AKsa6Qe7hQ688ZPuv-ykGR7MYF18NVa97Wcp_zx6UsvGw4s5LqLvnz5-O_2SbM4_r07LTaKylA9JoVNCESs40BRhqUOUkHKtaV2hVCFJADPMq4wzLqnKkeSSa0aIxJjIvKKL6PVet2-sF_M0vcBZznE4YXaLaLVHaCt3onemle6XsNKIvwnrtkK6wagGBOV5TWWqdZ0Cg8BnuQZSKAZVAXWhgtb7-bexakEr6AYnmwPRw5fOXIutvREslJxiFgROZgFnf4zgB9Ear6BpZAd2nOouEOYkR1mAvvkP-nB3M2orQwOmq234V02iomQU0bAYDajlA6iwNbRGBevVJuQPCGxPUM5676C-6xEjMRn3thgxGVfMxg20V_fnc0e6dSr9A4Ut6-g</recordid><startdate>20150506</startdate><enddate>20150506</enddate><creator>Herbert, Bethany A</creator><creator>Valerio, Michael S</creator><creator>Gaestel, Matthias</creator><creator>Kirkwood, Keith L</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150506</creationdate><title>Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations</title><author>Herbert, Bethany A ; Valerio, Michael S ; Gaestel, Matthias ; Kirkwood, Keith L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c659t-8d5230489e3501ad9e3ae59dd3fb05c0a2e1419b6949a3c70a9a9d422a112a7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acid phosphatase</topic><topic>Acid phosphatase (tartrate-resistant)</topic><topic>Acid Phosphatase - 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metabolism</topic><topic>Oral hygiene</topic><topic>Osteoclastogenesis</topic><topic>Osteoclasts</topic><topic>Osteoclasts (Biology)</topic><topic>Osteoclasts - cytology</topic><topic>Osteoclasts - metabolism</topic><topic>Osteoprogenitor cells</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Protein kinase</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>RANK Ligand - metabolism</topic><topic>Rodents</topic><topic>Sex Characteristics</topic><topic>Sexual dimorphism</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Stem Cells - cytology</topic><topic>Stimulation</topic><topic>Subpopulations</topic><topic>Substrates</topic><topic>Tartrate-Resistant Acid Phosphatase</topic><topic>TRANCE protein</topic><topic>Transcription factors</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Herbert, Bethany A</creatorcontrib><creatorcontrib>Valerio, Michael S</creatorcontrib><creatorcontrib>Gaestel, Matthias</creatorcontrib><creatorcontrib>Kirkwood, Keith L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Herbert, Bethany A</au><au>Valerio, Michael S</au><au>Gaestel, Matthias</au><au>Kirkwood, Keith L</au><au>Tintut, Yin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-06</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0125387</spage><epage>e0125387</epage><pages>e0125387-e0125387</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal integrity through coupled bone turnover. OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a specific subpopulation of defined osteoclast progenitor cells (dOCPs) with surface expression of B220(-)Gr1(-)CD11b(lo/-)CD115(+) (dOCP(lo/-)). In this study, we isolated dOCPs from male and female mice to determine sex-specific effects of MK2 signaling in osteoclastogenesis (OCgen). Male Mk2(-/-) mice display an increase in the dOCP(lo) cell population when compared to Mk2(+/+) mice, while female Mk2(-/-) and Mk2(+/+ )mice exhibit no difference. Defined OCPs from male and female Mk2(+/+) and Mk2(-/-) bone marrow were treated with macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote OCgen. RANKL treatment of dOCP(lo) cells stimulated p38 and MK2 phosphorylation. Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was critical for male dOCP(lo) OCgen, yet MK2 signaling regulated OCgen from female dOCP- and CD11b(hi) subpopulations as well. The functional gene, Ctsk, was attenuated in both male and female Mk2(-/-) dOCP(lo)-derived OCs. Conversely, MK2 signaling was only critical for gene expression of pre-OC fusion genes, Oc-stamp andTm7sf4, in male OCgen. Therefore, these data suggest there is a sexual dimorphism in MK2 signaling of OCP subpopulations.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25946081</pmid><doi>10.1371/journal.pone.0125387</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0125387-e0125387 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1679179119 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acid phosphatase Acid phosphatase (tartrate-resistant) Acid Phosphatase - metabolism Acid resistance Animals Arthritis Biochemistry Biocompatibility Biological research Bone marrow Bone Marrow Cells Bone turnover Cathepsin K - genetics CD11b antigen Cell cycle Cell Differentiation Cells (biology) Cells, Cultured Cytokines Dimorphism (Biology) Disease Enzymatic activity Enzyme activity Female Females Gender differences Gene expression Gene fusion Health sciences Inflammation Intracellular Signaling Peptides and Proteins - metabolism Isoenzymes - metabolism Kinases Ligands (Biochemistry) Macrophage colony-stimulating factor Macrophages Male MAP kinase Medical research Mice Mice, Inbred C57BL Mice, Knockout Mitogen-activated protein kinases NF-κB protein NFATC Transcription Factors - metabolism Oral hygiene Osteoclastogenesis Osteoclasts Osteoclasts (Biology) Osteoclasts - cytology Osteoclasts - metabolism Osteoprogenitor cells p38 Mitogen-Activated Protein Kinases - metabolism Phosphorylation Physiological aspects Physiology Protein kinase Protein-Serine-Threonine Kinases - metabolism Proteins RANK Ligand - metabolism Rodents Sex Characteristics Sexual dimorphism Signal Transduction Signaling Stem Cells - cytology Stimulation Subpopulations Substrates Tartrate-Resistant Acid Phosphatase TRANCE protein Transcription factors Womens health |
| title | Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations |
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