Tendons of myostatin-deficient mice are small, brittle, and hypocellular
Tendons play a significant role in the modulation of forces transmitted between bones and skeletal muscles and consequently protect muscle fibers from contraction-induced, or high-strain, injuries. Myostatin (GDF-8) is a negative regulator of muscle mass. Inhibition of myostatin not only increases t...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-01, Vol.105 (1), p.388-393 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 393 |
|---|---|
| container_issue | 1 |
| container_start_page | 388 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Mendias, Christopher L Bakhurin, Konstantin I Faulkner, John A |
| description | Tendons play a significant role in the modulation of forces transmitted between bones and skeletal muscles and consequently protect muscle fibers from contraction-induced, or high-strain, injuries. Myostatin (GDF-8) is a negative regulator of muscle mass. Inhibition of myostatin not only increases the mass and maximum isometric force of muscles, but also increases the susceptibility of muscle fibers to contraction-induced injury. We hypothesized that myostatin would regulate the morphology and mechanical properties of tendons. The expression of myostatin and the myostatin receptors ACVR2B and ACVRB was detectable in tendons. Surprisingly, compared with wild type (MSTN⁺/⁺) mice, the tendons of myostatin-null mice (MSTN⁻/⁻) were smaller and had a decrease in fibroblast density and a decrease in the expression of type I collagen. Tendons of MSTN⁻/⁻ mice also had a decrease in the expression of two genes that promote tendon fibroblast proliferation: scleraxis and tenomodulin. Treatment of tendon fibroblasts with myostatin activated the p38 MAPK and Smad2/3 signaling cascades, increased cell proliferation, and increased the expression of type I collagen, scleraxis, and tenomodulin. Compared with the tendons of MSTN⁺/⁺ mice, the mechanical properties of tibialis anterior tendons from MSTN⁻/⁻ mice had a greater peak stress, a lower peak strain, and increased stiffness. We conclude that, in addition to the regulation of muscle mass and force, myostatin regulates the structure and function of tendon tissues. |
| doi_str_mv | 10.1073/pnas.0707069105 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_fao_a</sourceid><recordid>TN_cdi_fao_agris_US201300845562</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>25451093</jstor_id><sourcerecordid>25451093</sourcerecordid><originalsourceid>FETCH-LOGICAL-c614t-16aa733ace2f18ea0b0491677f14a4ed73666024c015b99bcc57c08035dc8d573</originalsourceid><addsrcrecordid>eNqFkr1vFDEQxS0EIkegpgJWKaiyyfjb2yChCAhSJAqS2vJ5vYlP3vVhexH338fHnXKBAmRZLt5vnmbmGaHXGM4wSHq-nkw-A1mP6DDwJ2iBocOtYB08RQsAIlvFCDtCL3JeAUDHFTxHR1hhQTgnC3R57aY-TrmJQzNuYi6m-Knt3eCtd1NpRm9dY5Jr8mhCOG2WyZcS3Gljpr6526yjdSHMwaSX6NlgQnav9u8xuvn86frisr369uXrxcer1grMSouFMZJSYx0ZsHIGlsA6LKQcMDPM9ZIKIYAwC5gvu25pLZcWFFDeW9VzSY_Rh53vel6Orre1yWSCXic_mrTR0Xj9pzL5O30bf2pCCKu3GrzfG6T4Y3a56NHn7RRmcnHOWgLuiJT8vyABThX-7XjyF7iKc5rqFiqDiaopdBU630E2xZyTGx5axqC3WeptlvqQZa14-3jSA78P71GD28qDHddYU6X0MIdQ3K9SwTf_Ag_6KpeYHgDCGa_fiVb93U4fTNTmNvmsb77X0SiAYpwLQu8BtFrEAg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201280279</pqid></control><display><type>article</type><title>Tendons of myostatin-deficient mice are small, brittle, and hypocellular</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Mendias, Christopher L ; Bakhurin, Konstantin I ; Faulkner, John A</creator><creatorcontrib>Mendias, Christopher L ; Bakhurin, Konstantin I ; Faulkner, John A</creatorcontrib><description>Tendons play a significant role in the modulation of forces transmitted between bones and skeletal muscles and consequently protect muscle fibers from contraction-induced, or high-strain, injuries. Myostatin (GDF-8) is a negative regulator of muscle mass. Inhibition of myostatin not only increases the mass and maximum isometric force of muscles, but also increases the susceptibility of muscle fibers to contraction-induced injury. We hypothesized that myostatin would regulate the morphology and mechanical properties of tendons. The expression of myostatin and the myostatin receptors ACVR2B and ACVRB was detectable in tendons. Surprisingly, compared with wild type (MSTN⁺/⁺) mice, the tendons of myostatin-null mice (MSTN⁻/⁻) were smaller and had a decrease in fibroblast density and a decrease in the expression of type I collagen. Tendons of MSTN⁻/⁻ mice also had a decrease in the expression of two genes that promote tendon fibroblast proliferation: scleraxis and tenomodulin. Treatment of tendon fibroblasts with myostatin activated the p38 MAPK and Smad2/3 signaling cascades, increased cell proliferation, and increased the expression of type I collagen, scleraxis, and tenomodulin. Compared with the tendons of MSTN⁺/⁺ mice, the mechanical properties of tibialis anterior tendons from MSTN⁻/⁻ mice had a greater peak stress, a lower peak strain, and increased stiffness. We conclude that, in addition to the regulation of muscle mass and force, myostatin regulates the structure and function of tendon tissues.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0707069105</identifier><identifier>PMID: 18162552</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biological Sciences ; Collagens ; Comparative analysis ; Fibroblasts ; Gene expression ; Gene Expression Regulation ; Mechanical properties ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Biological ; Models, Genetic ; Muscle Fibers, Skeletal - metabolism ; Muscle, Skeletal - metabolism ; Muscles ; Muscles - pathology ; Musculoskeletal system ; Myostatin ; Receptors ; Rodents ; Skeletal muscle ; Sprains and strains ; Stiffness ; Tendons ; Tendons - abnormalities ; Tendons - pathology ; Tissues ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - physiology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-01, Vol.105 (1), p.388-393</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jan 8, 2008</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c614t-16aa733ace2f18ea0b0491677f14a4ed73666024c015b99bcc57c08035dc8d573</citedby><cites>FETCH-LOGICAL-c614t-16aa733ace2f18ea0b0491677f14a4ed73666024c015b99bcc57c08035dc8d573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/1.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25451093$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25451093$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18162552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mendias, Christopher L</creatorcontrib><creatorcontrib>Bakhurin, Konstantin I</creatorcontrib><creatorcontrib>Faulkner, John A</creatorcontrib><title>Tendons of myostatin-deficient mice are small, brittle, and hypocellular</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Tendons play a significant role in the modulation of forces transmitted between bones and skeletal muscles and consequently protect muscle fibers from contraction-induced, or high-strain, injuries. Myostatin (GDF-8) is a negative regulator of muscle mass. Inhibition of myostatin not only increases the mass and maximum isometric force of muscles, but also increases the susceptibility of muscle fibers to contraction-induced injury. We hypothesized that myostatin would regulate the morphology and mechanical properties of tendons. The expression of myostatin and the myostatin receptors ACVR2B and ACVRB was detectable in tendons. Surprisingly, compared with wild type (MSTN⁺/⁺) mice, the tendons of myostatin-null mice (MSTN⁻/⁻) were smaller and had a decrease in fibroblast density and a decrease in the expression of type I collagen. Tendons of MSTN⁻/⁻ mice also had a decrease in the expression of two genes that promote tendon fibroblast proliferation: scleraxis and tenomodulin. Treatment of tendon fibroblasts with myostatin activated the p38 MAPK and Smad2/3 signaling cascades, increased cell proliferation, and increased the expression of type I collagen, scleraxis, and tenomodulin. Compared with the tendons of MSTN⁺/⁺ mice, the mechanical properties of tibialis anterior tendons from MSTN⁻/⁻ mice had a greater peak stress, a lower peak strain, and increased stiffness. We conclude that, in addition to the regulation of muscle mass and force, myostatin regulates the structure and function of tendon tissues.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biological Sciences</subject><subject>Collagens</subject><subject>Comparative analysis</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Mechanical properties</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Models, Biological</subject><subject>Models, Genetic</subject><subject>Muscle Fibers, Skeletal - metabolism</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscles</subject><subject>Muscles - pathology</subject><subject>Musculoskeletal system</subject><subject>Myostatin</subject><subject>Receptors</subject><subject>Rodents</subject><subject>Skeletal muscle</subject><subject>Sprains and strains</subject><subject>Stiffness</subject><subject>Tendons</subject><subject>Tendons - abnormalities</subject><subject>Tendons - pathology</subject><subject>Tissues</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - physiology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkr1vFDEQxS0EIkegpgJWKaiyyfjb2yChCAhSJAqS2vJ5vYlP3vVhexH338fHnXKBAmRZLt5vnmbmGaHXGM4wSHq-nkw-A1mP6DDwJ2iBocOtYB08RQsAIlvFCDtCL3JeAUDHFTxHR1hhQTgnC3R57aY-TrmJQzNuYi6m-Knt3eCtd1NpRm9dY5Jr8mhCOG2WyZcS3Gljpr6526yjdSHMwaSX6NlgQnav9u8xuvn86frisr369uXrxcer1grMSouFMZJSYx0ZsHIGlsA6LKQcMDPM9ZIKIYAwC5gvu25pLZcWFFDeW9VzSY_Rh53vel6Orre1yWSCXic_mrTR0Xj9pzL5O30bf2pCCKu3GrzfG6T4Y3a56NHn7RRmcnHOWgLuiJT8vyABThX-7XjyF7iKc5rqFiqDiaopdBU630E2xZyTGx5axqC3WeptlvqQZa14-3jSA78P71GD28qDHddYU6X0MIdQ3K9SwTf_Ag_6KpeYHgDCGa_fiVb93U4fTNTmNvmsb77X0SiAYpwLQu8BtFrEAg</recordid><startdate>20080108</startdate><enddate>20080108</enddate><creator>Mendias, Christopher L</creator><creator>Bakhurin, Konstantin I</creator><creator>Faulkner, John A</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080108</creationdate><title>Tendons of myostatin-deficient mice are small, brittle, and hypocellular</title><author>Mendias, Christopher L ; Bakhurin, Konstantin I ; Faulkner, John A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c614t-16aa733ace2f18ea0b0491677f14a4ed73666024c015b99bcc57c08035dc8d573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biological Sciences</topic><topic>Collagens</topic><topic>Comparative analysis</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Mechanical properties</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Models, Biological</topic><topic>Models, Genetic</topic><topic>Muscle Fibers, Skeletal - metabolism</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscles</topic><topic>Muscles - pathology</topic><topic>Musculoskeletal system</topic><topic>Myostatin</topic><topic>Receptors</topic><topic>Rodents</topic><topic>Skeletal muscle</topic><topic>Sprains and strains</topic><topic>Stiffness</topic><topic>Tendons</topic><topic>Tendons - abnormalities</topic><topic>Tendons - pathology</topic><topic>Tissues</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mendias, Christopher L</creatorcontrib><creatorcontrib>Bakhurin, Konstantin I</creatorcontrib><creatorcontrib>Faulkner, John A</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mendias, Christopher L</au><au>Bakhurin, Konstantin I</au><au>Faulkner, John A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tendons of myostatin-deficient mice are small, brittle, and hypocellular</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2008-01-08</date><risdate>2008</risdate><volume>105</volume><issue>1</issue><spage>388</spage><epage>393</epage><pages>388-393</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Tendons play a significant role in the modulation of forces transmitted between bones and skeletal muscles and consequently protect muscle fibers from contraction-induced, or high-strain, injuries. Myostatin (GDF-8) is a negative regulator of muscle mass. Inhibition of myostatin not only increases the mass and maximum isometric force of muscles, but also increases the susceptibility of muscle fibers to contraction-induced injury. We hypothesized that myostatin would regulate the morphology and mechanical properties of tendons. The expression of myostatin and the myostatin receptors ACVR2B and ACVRB was detectable in tendons. Surprisingly, compared with wild type (MSTN⁺/⁺) mice, the tendons of myostatin-null mice (MSTN⁻/⁻) were smaller and had a decrease in fibroblast density and a decrease in the expression of type I collagen. Tendons of MSTN⁻/⁻ mice also had a decrease in the expression of two genes that promote tendon fibroblast proliferation: scleraxis and tenomodulin. Treatment of tendon fibroblasts with myostatin activated the p38 MAPK and Smad2/3 signaling cascades, increased cell proliferation, and increased the expression of type I collagen, scleraxis, and tenomodulin. Compared with the tendons of MSTN⁺/⁺ mice, the mechanical properties of tibialis anterior tendons from MSTN⁻/⁻ mice had a greater peak stress, a lower peak strain, and increased stiffness. We conclude that, in addition to the regulation of muscle mass and force, myostatin regulates the structure and function of tendon tissues.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>18162552</pmid><doi>10.1073/pnas.0707069105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2008-01, Vol.105 (1), p.388-393 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_fao_agris_US201300845562 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Basic Helix-Loop-Helix Transcription Factors - metabolism Biological Sciences Collagens Comparative analysis Fibroblasts Gene expression Gene Expression Regulation Mechanical properties Mice Mice, Inbred C57BL Mice, Transgenic Models, Biological Models, Genetic Muscle Fibers, Skeletal - metabolism Muscle, Skeletal - metabolism Muscles Muscles - pathology Musculoskeletal system Myostatin Receptors Rodents Skeletal muscle Sprains and strains Stiffness Tendons Tendons - abnormalities Tendons - pathology Tissues Transforming Growth Factor beta - genetics Transforming Growth Factor beta - physiology |
| title | Tendons of myostatin-deficient mice are small, brittle, and hypocellular |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T12%3A05%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_fao_a&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tendons%20of%20myostatin-deficient%20mice%20are%20small,%20brittle,%20and%20hypocellular&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Mendias,%20Christopher%20L&rft.date=2008-01-08&rft.volume=105&rft.issue=1&rft.spage=388&rft.epage=393&rft.pages=388-393&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0707069105&rft_dat=%3Cjstor_fao_a%3E25451093%3C/jstor_fao_a%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201280279&rft_id=info:pmid/18162552&rft_jstor_id=25451093&rfr_iscdi=true |