Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification
Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is c...
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| Veröffentlicht in: | The Journal of experimental medicine 2007-07, Vol.204 (7), p.1613-1623 |
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| creator | Morita, Kozo Miyamoto, Takeshi Fujita, Nobuyuki Kubota, Yoshiaki Ito, Keisuke Takubo, Keiyo Miyamoto, Kana Ninomiya, Ken Suzuki, Toru Iwasaki, Ryotaro Yagi, Mitsuru Takaishi, Hironari Toyama, Yoshiaki Suda, Toshio |
| description | Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)-deficient (Atm(-/-)) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm(-/-) mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes. |
| doi_str_mv | 10.1084/jem.20062525 |
| format | Article |
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Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)-deficient (Atm(-/-)) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm(-/-) mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>EISSN: 1892-1007</identifier><identifier>DOI: 10.1084/jem.20062525</identifier><identifier>PMID: 17576777</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Acetylcysteine - pharmacology ; Animals ; Antioxidants - pharmacology ; Ataxia Telangiectasia Mutated Proteins ; Calcification, Physiologic - drug effects ; Calcification, Physiologic - physiology ; Cell Cycle Proteins - genetics ; Cell Differentiation - drug effects ; Cell Differentiation - physiology ; Cell Division ; Cell Line ; Chondrocytes - cytology ; Chondrocytes - drug effects ; Chondrocytes - pathology ; DNA-Binding Proteins - deficiency ; DNA-Binding Proteins - genetics ; Hypertrophy ; Mice ; Mice, Knockout ; Neovascularization, Physiologic - drug effects ; Protein-Serine-Threonine Kinases - deficiency ; Protein-Serine-Threonine Kinases - genetics ; Reactive Oxygen Species - metabolism ; Reactive Oxygen Species - pharmacology ; Tumor Suppressor Proteins - deficiency ; Tumor Suppressor Proteins - genetics</subject><ispartof>The Journal of experimental medicine, 2007-07, Vol.204 (7), p.1613-1623</ispartof><rights>Copyright © 2007, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-c8cff76007601469d8e4e0dc218eb0bca64e26b69e628c3720d14754924ca92a3</citedby><cites>FETCH-LOGICAL-c479t-c8cff76007601469d8e4e0dc218eb0bca64e26b69e628c3720d14754924ca92a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17576777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morita, Kozo</creatorcontrib><creatorcontrib>Miyamoto, Takeshi</creatorcontrib><creatorcontrib>Fujita, Nobuyuki</creatorcontrib><creatorcontrib>Kubota, Yoshiaki</creatorcontrib><creatorcontrib>Ito, Keisuke</creatorcontrib><creatorcontrib>Takubo, Keiyo</creatorcontrib><creatorcontrib>Miyamoto, Kana</creatorcontrib><creatorcontrib>Ninomiya, Ken</creatorcontrib><creatorcontrib>Suzuki, Toru</creatorcontrib><creatorcontrib>Iwasaki, Ryotaro</creatorcontrib><creatorcontrib>Yagi, Mitsuru</creatorcontrib><creatorcontrib>Takaishi, Hironari</creatorcontrib><creatorcontrib>Toyama, Yoshiaki</creatorcontrib><creatorcontrib>Suda, Toshio</creatorcontrib><title>Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)-deficient (Atm(-/-)) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm(-/-) mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.</description><subject>Acetylcysteine - pharmacology</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Ataxia Telangiectasia Mutated Proteins</subject><subject>Calcification, Physiologic - drug effects</subject><subject>Calcification, Physiologic - physiology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Division</subject><subject>Cell Line</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - drug effects</subject><subject>Chondrocytes - pathology</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Hypertrophy</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Protein-Serine-Threonine Kinases - deficiency</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Reactive Oxygen Species - pharmacology</subject><subject>Tumor Suppressor Proteins - deficiency</subject><subject>Tumor Suppressor Proteins - genetics</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1892-1007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtLxDAUhYMozji6cy1dubJjkqZJuxFk8AUDgo91SNPbaYa2qU072H9vZMbXSu7iLs7H4dx7EDoleE5wwi7XUM8pxpzGNN5DUxIzHKZxlOyjKcaUhgRjMUFHzq0xJozF_BBNiIgFF0JM0fMTKN2bDQT2fVxBE7gWtAEXmCYfNAS6tE3eWT32EJRjC13f2bYcvRxAk9utrKrAOmcKo1VvbHOMDgpVOTjZ7Rl6vb15WdyHy8e7h8X1MtRMpH2oE10Ugvt43AfjaZ4AA5xrShLIcKYVZ0B5xlPgNNGRoDgnTMQspUyrlKpohq62vu2Q1ZBraHofRbadqVU3SquM_Ks0ppQru5GUkISzyBuc7ww6-zaA62VtnIaqUg3YwUmB_dBY_AuSVNCUEebBiy2oO_-RDorvNATLz7qkr0t-1eXxs98X_MC7fqIPeJOTBw</recordid><startdate>20070709</startdate><enddate>20070709</enddate><creator>Morita, Kozo</creator><creator>Miyamoto, Takeshi</creator><creator>Fujita, Nobuyuki</creator><creator>Kubota, Yoshiaki</creator><creator>Ito, Keisuke</creator><creator>Takubo, Keiyo</creator><creator>Miyamoto, Kana</creator><creator>Ninomiya, Ken</creator><creator>Suzuki, Toru</creator><creator>Iwasaki, Ryotaro</creator><creator>Yagi, Mitsuru</creator><creator>Takaishi, Hironari</creator><creator>Toyama, Yoshiaki</creator><creator>Suda, Toshio</creator><general>The Rockefeller University Press</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>7QP</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070709</creationdate><title>Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification</title><author>Morita, Kozo ; Miyamoto, Takeshi ; Fujita, Nobuyuki ; Kubota, Yoshiaki ; Ito, Keisuke ; Takubo, Keiyo ; Miyamoto, Kana ; Ninomiya, Ken ; Suzuki, Toru ; Iwasaki, Ryotaro ; Yagi, Mitsuru ; Takaishi, Hironari ; Toyama, Yoshiaki ; Suda, Toshio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-c8cff76007601469d8e4e0dc218eb0bca64e26b69e628c3720d14754924ca92a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acetylcysteine - pharmacology</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Ataxia Telangiectasia Mutated Proteins</topic><topic>Calcification, Physiologic - drug effects</topic><topic>Calcification, Physiologic - physiology</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Division</topic><topic>Cell Line</topic><topic>Chondrocytes - cytology</topic><topic>Chondrocytes - drug effects</topic><topic>Chondrocytes - pathology</topic><topic>DNA-Binding Proteins - deficiency</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Hypertrophy</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Protein-Serine-Threonine Kinases - deficiency</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Reactive Oxygen Species - pharmacology</topic><topic>Tumor Suppressor Proteins - deficiency</topic><topic>Tumor Suppressor Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morita, Kozo</creatorcontrib><creatorcontrib>Miyamoto, Takeshi</creatorcontrib><creatorcontrib>Fujita, Nobuyuki</creatorcontrib><creatorcontrib>Kubota, Yoshiaki</creatorcontrib><creatorcontrib>Ito, Keisuke</creatorcontrib><creatorcontrib>Takubo, Keiyo</creatorcontrib><creatorcontrib>Miyamoto, Kana</creatorcontrib><creatorcontrib>Ninomiya, Ken</creatorcontrib><creatorcontrib>Suzuki, Toru</creatorcontrib><creatorcontrib>Iwasaki, Ryotaro</creatorcontrib><creatorcontrib>Yagi, Mitsuru</creatorcontrib><creatorcontrib>Takaishi, Hironari</creatorcontrib><creatorcontrib>Toyama, Yoshiaki</creatorcontrib><creatorcontrib>Suda, Toshio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morita, Kozo</au><au>Miyamoto, Takeshi</au><au>Fujita, Nobuyuki</au><au>Kubota, Yoshiaki</au><au>Ito, Keisuke</au><au>Takubo, Keiyo</au><au>Miyamoto, Kana</au><au>Ninomiya, Ken</au><au>Suzuki, Toru</au><au>Iwasaki, Ryotaro</au><au>Yagi, Mitsuru</au><au>Takaishi, Hironari</au><au>Toyama, Yoshiaki</au><au>Suda, Toshio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2007-07-09</date><risdate>2007</risdate><volume>204</volume><issue>7</issue><spage>1613</spage><epage>1623</epage><pages>1613-1623</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><eissn>1892-1007</eissn><abstract>Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)-deficient (Atm(-/-)) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm(-/-) mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>17576777</pmid><doi>10.1084/jem.20062525</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcysteine - pharmacology Animals Antioxidants - pharmacology Ataxia Telangiectasia Mutated Proteins Calcification, Physiologic - drug effects Calcification, Physiologic - physiology Cell Cycle Proteins - genetics Cell Differentiation - drug effects Cell Differentiation - physiology Cell Division Cell Line Chondrocytes - cytology Chondrocytes - drug effects Chondrocytes - pathology DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics Hypertrophy Mice Mice, Knockout Neovascularization, Physiologic - drug effects Protein-Serine-Threonine Kinases - deficiency Protein-Serine-Threonine Kinases - genetics Reactive Oxygen Species - metabolism Reactive Oxygen Species - pharmacology Tumor Suppressor Proteins - deficiency Tumor Suppressor Proteins - genetics |
| title | Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification |
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