In Vivo Analysis of Arg‐Gly‐Asp Sequence/Integrin α5β1‐Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System
ABSTRACT Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin α5β1–ligand interactions inhibited pre‐hypertrophic chondroc...
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| Veröffentlicht in: | Journal of bone and mineral research 2014-07, Vol.29 (7), p.1554-1563 |
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| creator | Inoue, Takayuki Hashimoto, Ryuju Matsumoto, Akihiro Jahan, Esrat Rafiq, Ashiq Mahmood Udagawa, Jun Hatta, Toshihisa Otani, Hiroki |
| description | ABSTRACT
Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin α5β1–ligand interactions inhibited pre‐hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin α5β1‐mediated signal through the Arg‐Gly‐Asp (RGD) sequence in the cell–extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg‐Gly‐Asp‐Ser (RGDS) peptides and anti‐integrin α5β1 antibody (α5β1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS‐injected limbs, α5β1 ab‐injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg‐Gly‐Glu‐Ser peptide‐, mouse IgG‐, or vehicle‐injected, and no surgery) at E16.5. In the RGDS‐injected limbs, the humeri were shorter and there were fewer BrdU‐positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS‐injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS‐injected limbs. In those limbs, TUNEL‐positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the α5β1 ab‐injected limbs showed results similar to those of RGDS‐injected limbs. The present in vivo study by exo utero development system showed that RGDS and α5β1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin α5β1‐mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification. © 2014 American Society for Bone and Mineral Research. |
| doi_str_mv | 10.1002/jbmr.2166 |
| format | Article |
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Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin α5β1–ligand interactions inhibited pre‐hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin α5β1‐mediated signal through the Arg‐Gly‐Asp (RGD) sequence in the cell–extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg‐Gly‐Asp‐Ser (RGDS) peptides and anti‐integrin α5β1 antibody (α5β1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS‐injected limbs, α5β1 ab‐injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg‐Gly‐Glu‐Ser peptide‐, mouse IgG‐, or vehicle‐injected, and no surgery) at E16.5. In the RGDS‐injected limbs, the humeri were shorter and there were fewer BrdU‐positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS‐injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS‐injected limbs. In those limbs, TUNEL‐positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the α5β1 ab‐injected limbs showed results similar to those of RGDS‐injected limbs. The present in vivo study by exo utero development system showed that RGDS and α5β1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin α5β1‐mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification. © 2014 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.2166</identifier><identifier>PMID: 24375788</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antibodies - pharmacology ; APOPTOSIS ; Body Weight - drug effects ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; CHONDROCYTES ; Chondrocytes - cytology ; Chondrocytes - drug effects ; COLLAGEN ; Crown-Rump Length ; EMBRYO ; Embryo, Mammalian - metabolism ; Embryonic Development - drug effects ; Extremities - embryology ; Female ; Growth Plate - drug effects ; Growth Plate - embryology ; Injections ; INTEGRIN ; Integrin alpha5beta1 - chemistry ; Integrin alpha5beta1 - metabolism ; Mice ; Oligopeptides - metabolism ; Oligopeptides - pharmacology ; Osteogenesis - drug effects ; Signal Transduction - drug effects</subject><ispartof>Journal of bone and mineral research, 2014-07, Vol.29 (7), p.1554-1563</ispartof><rights>2014 American Society for Bone and Mineral Research</rights><rights>2014 American Society for Bone and Mineral Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4996-c874b061842e66f2123e160c575cda396951b4303ef38c4b3b5c42b8e582143</citedby><cites>FETCH-LOGICAL-c4996-c874b061842e66f2123e160c575cda396951b4303ef38c4b3b5c42b8e582143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.2166$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.2166$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24375788$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inoue, Takayuki</creatorcontrib><creatorcontrib>Hashimoto, Ryuju</creatorcontrib><creatorcontrib>Matsumoto, Akihiro</creatorcontrib><creatorcontrib>Jahan, Esrat</creatorcontrib><creatorcontrib>Rafiq, Ashiq Mahmood</creatorcontrib><creatorcontrib>Udagawa, Jun</creatorcontrib><creatorcontrib>Hatta, Toshihisa</creatorcontrib><creatorcontrib>Otani, Hiroki</creatorcontrib><title>In Vivo Analysis of Arg‐Gly‐Asp Sequence/Integrin α5β1‐Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT
Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin α5β1–ligand interactions inhibited pre‐hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin α5β1‐mediated signal through the Arg‐Gly‐Asp (RGD) sequence in the cell–extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg‐Gly‐Asp‐Ser (RGDS) peptides and anti‐integrin α5β1 antibody (α5β1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS‐injected limbs, α5β1 ab‐injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg‐Gly‐Glu‐Ser peptide‐, mouse IgG‐, or vehicle‐injected, and no surgery) at E16.5. In the RGDS‐injected limbs, the humeri were shorter and there were fewer BrdU‐positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS‐injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS‐injected limbs. In those limbs, TUNEL‐positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the α5β1 ab‐injected limbs showed results similar to those of RGDS‐injected limbs. The present in vivo study by exo utero development system showed that RGDS and α5β1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin α5β1‐mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification. © 2014 American Society for Bone and Mineral Research.</description><subject>Animals</subject><subject>Antibodies - pharmacology</subject><subject>APOPTOSIS</subject><subject>Body Weight - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>CHONDROCYTES</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - drug effects</subject><subject>COLLAGEN</subject><subject>Crown-Rump Length</subject><subject>EMBRYO</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryonic Development - drug effects</subject><subject>Extremities - embryology</subject><subject>Female</subject><subject>Growth Plate - drug effects</subject><subject>Growth Plate - embryology</subject><subject>Injections</subject><subject>INTEGRIN</subject><subject>Integrin alpha5beta1 - chemistry</subject><subject>Integrin alpha5beta1 - metabolism</subject><subject>Mice</subject><subject>Oligopeptides - metabolism</subject><subject>Oligopeptides - pharmacology</subject><subject>Osteogenesis - drug effects</subject><subject>Signal Transduction - drug effects</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u00AQh1cIREPhwAugPcLBzf73-hhK2ga1qkSAq2Wvx2ErezfsOqG-8Qi8Ac9QHqQPwZN005TeuMwc5ptPmvkh9JqSI0oIm17VfThiVKknaEIl45lQmj5FE6K1yIjg9AC9iPGKEKKkUs_RARM8l7nWE_R74fBXu_V45qpujDZi3-JZWP39-eu0G1OdxTVewvcNOAPThRtgFazDtzfy9g9N4wtobDVAg5d2lQx44ba-20IPbsCJm_d1GL2zBs-d-eZdExJzGaNtrakG6x2uRzy_9vjLAMHjD7CFzq_vt5djHKB_iZ61VRfh1UM_RMuT-efjs-z88nRxPDvPjCgKlRmdi5ooqgUDpVpGGQeqiJG5NE3FC1VIWgtOOLRcG1HzWhrBag1SMyr4IXq7t66DT6fGoextNNB1lQO_iSWVgvKcFCJP6Ls9aoKPMUBbroPtqzCWlJS7NMpdGuUujcS-edBu6h6aR_Lf-xMw3QM_bAfj_03lx_cXn-6VdzmfmfY</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Inoue, Takayuki</creator><creator>Hashimoto, Ryuju</creator><creator>Matsumoto, Akihiro</creator><creator>Jahan, Esrat</creator><creator>Rafiq, Ashiq Mahmood</creator><creator>Udagawa, Jun</creator><creator>Hatta, Toshihisa</creator><creator>Otani, Hiroki</creator><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>7X8</scope></search><sort><creationdate>201407</creationdate><title>In Vivo Analysis of Arg‐Gly‐Asp Sequence/Integrin α5β1‐Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System</title><author>Inoue, Takayuki ; Hashimoto, Ryuju ; Matsumoto, Akihiro ; Jahan, Esrat ; Rafiq, Ashiq Mahmood ; Udagawa, Jun ; Hatta, Toshihisa ; Otani, Hiroki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4996-c874b061842e66f2123e160c575cda396951b4303ef38c4b3b5c42b8e582143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antibodies - pharmacology</topic><topic>APOPTOSIS</topic><topic>Body Weight - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>CHONDROCYTES</topic><topic>Chondrocytes - cytology</topic><topic>Chondrocytes - drug effects</topic><topic>COLLAGEN</topic><topic>Crown-Rump Length</topic><topic>EMBRYO</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryonic Development - drug effects</topic><topic>Extremities - embryology</topic><topic>Female</topic><topic>Growth Plate - drug effects</topic><topic>Growth Plate - embryology</topic><topic>Injections</topic><topic>INTEGRIN</topic><topic>Integrin alpha5beta1 - chemistry</topic><topic>Integrin alpha5beta1 - metabolism</topic><topic>Mice</topic><topic>Oligopeptides - metabolism</topic><topic>Oligopeptides - pharmacology</topic><topic>Osteogenesis - drug effects</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inoue, Takayuki</creatorcontrib><creatorcontrib>Hashimoto, Ryuju</creatorcontrib><creatorcontrib>Matsumoto, Akihiro</creatorcontrib><creatorcontrib>Jahan, Esrat</creatorcontrib><creatorcontrib>Rafiq, Ashiq Mahmood</creatorcontrib><creatorcontrib>Udagawa, Jun</creatorcontrib><creatorcontrib>Hatta, Toshihisa</creatorcontrib><creatorcontrib>Otani, Hiroki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inoue, Takayuki</au><au>Hashimoto, Ryuju</au><au>Matsumoto, Akihiro</au><au>Jahan, Esrat</au><au>Rafiq, Ashiq Mahmood</au><au>Udagawa, Jun</au><au>Hatta, Toshihisa</au><au>Otani, Hiroki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vivo Analysis of Arg‐Gly‐Asp Sequence/Integrin α5β1‐Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2014-07</date><risdate>2014</risdate><volume>29</volume><issue>7</issue><spage>1554</spage><epage>1563</epage><pages>1554-1563</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><abstract>ABSTRACT
Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin α5β1–ligand interactions inhibited pre‐hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin α5β1‐mediated signal through the Arg‐Gly‐Asp (RGD) sequence in the cell–extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg‐Gly‐Asp‐Ser (RGDS) peptides and anti‐integrin α5β1 antibody (α5β1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS‐injected limbs, α5β1 ab‐injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg‐Gly‐Glu‐Ser peptide‐, mouse IgG‐, or vehicle‐injected, and no surgery) at E16.5. In the RGDS‐injected limbs, the humeri were shorter and there were fewer BrdU‐positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS‐injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS‐injected limbs. In those limbs, TUNEL‐positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the α5β1 ab‐injected limbs showed results similar to those of RGDS‐injected limbs. The present in vivo study by exo utero development system showed that RGDS and α5β1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin α5β1‐mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification. © 2014 American Society for Bone and Mineral Research.</abstract><cop>United States</cop><pmid>24375788</pmid><doi>10.1002/jbmr.2166</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies - pharmacology APOPTOSIS Body Weight - drug effects Cell Differentiation - drug effects Cell Proliferation - drug effects CHONDROCYTES Chondrocytes - cytology Chondrocytes - drug effects COLLAGEN Crown-Rump Length EMBRYO Embryo, Mammalian - metabolism Embryonic Development - drug effects Extremities - embryology Female Growth Plate - drug effects Growth Plate - embryology Injections INTEGRIN Integrin alpha5beta1 - chemistry Integrin alpha5beta1 - metabolism Mice Oligopeptides - metabolism Oligopeptides - pharmacology Osteogenesis - drug effects Signal Transduction - drug effects |
| title | In Vivo Analysis of Arg‐Gly‐Asp Sequence/Integrin α5β1‐Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System |
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