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TMJ Development and Growth Require Primary Cilia Function
Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia...
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| Published in: | Journal of dental research 2011-08, Vol.90 (8), p.988-994 |
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| container_end_page | 994 |
| container_issue | 8 |
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| container_title | Journal of dental research |
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| creator | Kinumatsu, T. Shibukawa, Y. Yasuda, T. Nagayama, M. Yamada, S. Serra, R. Pacifici, M. Koyama, E. |
| description | Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction. |
| doi_str_mv | 10.1177/0022034511409407 |
| format | article |
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Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction.</description><identifier>ISSN: 0022-0345</identifier><identifier>EISSN: 1544-0591</identifier><identifier>DOI: 10.1177/0022034511409407</identifier><identifier>PMID: 21566205</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Biological and medical sciences ; Bone growth ; Cartilage ; Cartilage, Articular - metabolism ; Cells, Cultured ; Chondrocytes ; Chondrocytes - cytology ; Chondrogenesis - genetics ; Cilia ; Cilia - physiology ; Collagen (type I) ; Collagen Type I - genetics ; Collagen Type I - metabolism ; Dentistry ; Embryology: invertebrates and vertebrates. Teratology ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Developmental ; Growth Plate - metabolism ; Hedgehog protein ; Hedgehog Proteins - genetics ; Hedgehog Proteins - physiology ; Intramembraneous bone ; Kinesin - genetics ; Kinesin - physiology ; Mandibular Condyle - growth & development ; Mice ; Mice, Knockout ; Mitosis ; Organogenesis. Physiological fonctions ; Ossification ; Ossification, Heterotopic - genetics ; Osteogenesis ; Osteogenesis - genetics ; Patched protein ; Patched Receptors ; Patched-1 Receptor ; Perichondrium ; Protein transport ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - physiology ; Signal Transduction ; Sox9 protein ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - physiology ; Sp7 Transcription Factor ; Temporomandibular joint ; Temporomandibular Joint - growth & development ; Transcription Factors - genetics ; Transcription Factors - physiology</subject><ispartof>Journal of dental research, 2011-08, Vol.90 (8), p.988-994</ispartof><rights>2011 International & American Associations for Dental Research</rights><rights>2015 INIST-CNRS</rights><rights>2011 International & American Associations for Dental Research 2011 International & American Associations for Dental Research</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-a5609e73eb0e660ea25cf44276e0f86903810366b8d72fba618b5052ff62ba623</citedby><cites>FETCH-LOGICAL-c557t-a5609e73eb0e660ea25cf44276e0f86903810366b8d72fba618b5052ff62ba623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24475733$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21566205$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kinumatsu, T.</creatorcontrib><creatorcontrib>Shibukawa, Y.</creatorcontrib><creatorcontrib>Yasuda, T.</creatorcontrib><creatorcontrib>Nagayama, M.</creatorcontrib><creatorcontrib>Yamada, S.</creatorcontrib><creatorcontrib>Serra, R.</creatorcontrib><creatorcontrib>Pacifici, M.</creatorcontrib><creatorcontrib>Koyama, E.</creatorcontrib><title>TMJ Development and Growth Require Primary Cilia Function</title><title>Journal of dental research</title><addtitle>J Dent Res</addtitle><description>Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone growth</subject><subject>Cartilage</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cells, Cultured</subject><subject>Chondrocytes</subject><subject>Chondrocytes - cytology</subject><subject>Chondrogenesis - genetics</subject><subject>Cilia</subject><subject>Cilia - physiology</subject><subject>Collagen (type I)</subject><subject>Collagen Type I - genetics</subject><subject>Collagen Type I - metabolism</subject><subject>Dentistry</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Growth Plate - metabolism</subject><subject>Hedgehog protein</subject><subject>Hedgehog Proteins - genetics</subject><subject>Hedgehog Proteins - physiology</subject><subject>Intramembraneous bone</subject><subject>Kinesin - genetics</subject><subject>Kinesin - physiology</subject><subject>Mandibular Condyle - growth & development</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitosis</subject><subject>Organogenesis. Physiological fonctions</subject><subject>Ossification</subject><subject>Ossification, Heterotopic - genetics</subject><subject>Osteogenesis</subject><subject>Osteogenesis - genetics</subject><subject>Patched protein</subject><subject>Patched Receptors</subject><subject>Patched-1 Receptor</subject><subject>Perichondrium</subject><subject>Protein transport</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - physiology</subject><subject>Signal Transduction</subject><subject>Sox9 protein</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>SOX9 Transcription Factor - physiology</subject><subject>Sp7 Transcription Factor</subject><subject>Temporomandibular joint</subject><subject>Temporomandibular Joint - growth & development</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><issn>0022-0345</issn><issn>1544-0591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp1kd1LHDEUxUNRdLv63icZkNKn0ZvvmRdBtt1tRVGKfQ6Z2TtultnJmsxY-t83y67aCj6EEM7vnpzLIeQThTNKtT4HYAy4kJQKKAXoD2REpRA5yJLukdFGzjf6IfkY4xKAlqzgB-SQUakUAzki5f3NVfYVn7D16xV2fWa7eTYL_ne_yH7i4-ACZnfBrWz4k01c62w2Hbq6d747IvuNbSMe7-4x-TX9dj_5nl_fzn5MLq_zWkrd51YqKFFzrACVArRM1o0QTCuEplAl8IICV6oq5po1lVW0qCRI1jSKpRfjY3Kx9V0P1QrndQoZbGvW21DGW2f-Vzq3MA_-ySjNinSSwZedQfCPA8berFyssW1th36IptCq4KxMScbk9A259EPo0naGcQBFBS11omBL1cHHGLB5yULBbGoxb2tJIyf_7vAy8NxDAj7vABtr2zbBdrWLr5wQWmrOE5dvuWgf8DXdux__BWPNn3Q</recordid><startdate>20110801</startdate><enddate>20110801</enddate><creator>Kinumatsu, T.</creator><creator>Shibukawa, Y.</creator><creator>Yasuda, T.</creator><creator>Nagayama, M.</creator><creator>Yamada, S.</creator><creator>Serra, R.</creator><creator>Pacifici, M.</creator><creator>Koyama, E.</creator><general>SAGE Publications</general><general>International Association for Dental Research</general><general>SAGE PUBLICATIONS, INC</general><scope>IQODW</scope><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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110801</creationdate><title>TMJ Development and Growth Require Primary Cilia Function</title><author>Kinumatsu, T. ; Shibukawa, Y. ; Yasuda, T. ; Nagayama, M. ; Yamada, S. ; Serra, R. ; Pacifici, M. ; Koyama, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-a5609e73eb0e660ea25cf44276e0f86903810366b8d72fba618b5052ff62ba623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone growth</topic><topic>Cartilage</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cells, Cultured</topic><topic>Chondrocytes</topic><topic>Chondrocytes - cytology</topic><topic>Chondrogenesis - genetics</topic><topic>Cilia</topic><topic>Cilia - physiology</topic><topic>Collagen (type I)</topic><topic>Collagen Type I - genetics</topic><topic>Collagen Type I - metabolism</topic><topic>Dentistry</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Growth Plate - metabolism</topic><topic>Hedgehog protein</topic><topic>Hedgehog Proteins - genetics</topic><topic>Hedgehog Proteins - physiology</topic><topic>Intramembraneous bone</topic><topic>Kinesin - genetics</topic><topic>Kinesin - physiology</topic><topic>Mandibular Condyle - growth & development</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitosis</topic><topic>Organogenesis. Physiological fonctions</topic><topic>Ossification</topic><topic>Ossification, Heterotopic - genetics</topic><topic>Osteogenesis</topic><topic>Osteogenesis - genetics</topic><topic>Patched protein</topic><topic>Patched Receptors</topic><topic>Patched-1 Receptor</topic><topic>Perichondrium</topic><topic>Protein transport</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - physiology</topic><topic>Signal Transduction</topic><topic>Sox9 protein</topic><topic>SOX9 Transcription Factor - genetics</topic><topic>SOX9 Transcription Factor - physiology</topic><topic>Sp7 Transcription Factor</topic><topic>Temporomandibular joint</topic><topic>Temporomandibular Joint - growth & development</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kinumatsu, T.</creatorcontrib><creatorcontrib>Shibukawa, Y.</creatorcontrib><creatorcontrib>Yasuda, T.</creatorcontrib><creatorcontrib>Nagayama, M.</creatorcontrib><creatorcontrib>Yamada, S.</creatorcontrib><creatorcontrib>Serra, R.</creatorcontrib><creatorcontrib>Pacifici, M.</creatorcontrib><creatorcontrib>Koyama, E.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of dental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kinumatsu, T.</au><au>Shibukawa, Y.</au><au>Yasuda, T.</au><au>Nagayama, M.</au><au>Yamada, S.</au><au>Serra, R.</au><au>Pacifici, M.</au><au>Koyama, E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TMJ Development and Growth Require Primary Cilia Function</atitle><jtitle>Journal of dental research</jtitle><addtitle>J Dent Res</addtitle><date>2011-08-01</date><risdate>2011</risdate><volume>90</volume><issue>8</issue><spage>988</spage><epage>994</epage><pages>988-994</pages><issn>0022-0345</issn><eissn>1544-0591</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>21566205</pmid><doi>10.1177/0022034511409407</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Bone growth Cartilage Cartilage, Articular - metabolism Cells, Cultured Chondrocytes Chondrocytes - cytology Chondrogenesis - genetics Cilia Cilia - physiology Collagen (type I) Collagen Type I - genetics Collagen Type I - metabolism Dentistry Embryology: invertebrates and vertebrates. Teratology Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Developmental Growth Plate - metabolism Hedgehog protein Hedgehog Proteins - genetics Hedgehog Proteins - physiology Intramembraneous bone Kinesin - genetics Kinesin - physiology Mandibular Condyle - growth & development Mice Mice, Knockout Mitosis Organogenesis. Physiological fonctions Ossification Ossification, Heterotopic - genetics Osteogenesis Osteogenesis - genetics Patched protein Patched Receptors Patched-1 Receptor Perichondrium Protein transport Receptors, Cell Surface - genetics Receptors, Cell Surface - physiology Signal Transduction Sox9 protein SOX9 Transcription Factor - genetics SOX9 Transcription Factor - physiology Sp7 Transcription Factor Temporomandibular joint Temporomandibular Joint - growth & development Transcription Factors - genetics Transcription Factors - physiology |
| title | TMJ Development and Growth Require Primary Cilia Function |
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