Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats
Introduction Haemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed. Aim To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage. Methods...
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| Veröffentlicht in: | Haemophilia : the official journal of the World Federation of Hemophilia 2020-05, Vol.26 (3), p.e88-e96 |
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| creator | Pulles, Astrid E. Vøls, Kåre K. Christensen, Kristine R. Coeleveld, Katja Hansen, Axel K. Vulpen, Lize F. D. Petersen, Maj Mastbergen, Simon C. Roepstorff, Kirstine Schutgens, Roger E. G. Kjelgaard‐Hansen, Mads Lafeber, Floris P. J. G. |
| description | Introduction
Haemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed.
Aim
To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage.
Methods
The 35Sulphate incorporation (35SO42− assay) was applied to tibial and patellar cartilage of wild‐type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4‐day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII‐deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro‐CT). Four‐ and 16‐day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the 35SO42− assay, with the contralateral knee as control.
Results
In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood‐exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood‐exposed knee.
Conclusion
For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the 35SO42− assay in a haemophilic rat model, establishing this assay as a novel method to study blood‐induced cartilage damage. |
| doi_str_mv | 10.1111/hae.13969 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7318356</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2383525031</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5099-34563e00848c754dae75fa1a886c6809e12025b05710d7ed08677c633a0a26a53</originalsourceid><addsrcrecordid>eNp1kb9uFDEQh1cIRMJBwQsgSzRQbOI_Z6-3QYqiQJAiQQG1NWfP3Try2oe9G3QdLV2eMU-Cw4UoIOHGY_nTN2P_muYlo0esruMB8IiJXvWPmkMmlGy5ZOrxbS1ZqzlTB82zUi4pZYJT9bQ5EJwzLhQ_bH5-zmnCtAk7C5GUXZwGLL6QDBMSKARITFcYyIjTkByZUq2gzBnJKqTkbn5c--hmi45YyJMPsEHicIMRq8GnSHyshli5OuSYtoMP3hKIjjw8V7Y8b56sIRR8cbcvmq_vz76cnrcXnz58PD25aK2kfd-KpVQCKdVLbTu5dICdXAMDrZVVmvbIOOVyRWXHqOvQUa26ziohgAJXIMWiebf3bufViM5inDIEs81-hLwzCbz5-yb6wWzSlekE06I2XzRv7gQ5fZuxTGb0xWIIEDHNxXBRMS6pYBV9_Q96meYc6_MMX1LV6U5zXqm3e8rmVErG9f0wjJrbgE39K_M74Mq-ejj9Pfkn0Qoc74HvPuDu_yZzfnK2V_4CadOzcw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2406787822</pqid></control><display><type>article</type><title>Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Pulles, Astrid E. ; Vøls, Kåre K. ; Christensen, Kristine R. ; Coeleveld, Katja ; Hansen, Axel K. ; Vulpen, Lize F. D. ; Petersen, Maj ; Mastbergen, Simon C. ; Roepstorff, Kirstine ; Schutgens, Roger E. G. ; Kjelgaard‐Hansen, Mads ; Lafeber, Floris P. J. G.</creator><creatorcontrib>Pulles, Astrid E. ; Vøls, Kåre K. ; Christensen, Kristine R. ; Coeleveld, Katja ; Hansen, Axel K. ; Vulpen, Lize F. D. ; Petersen, Maj ; Mastbergen, Simon C. ; Roepstorff, Kirstine ; Schutgens, Roger E. G. ; Kjelgaard‐Hansen, Mads ; Lafeber, Floris P. J. G.</creatorcontrib><description>Introduction
Haemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed.
Aim
To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage.
Methods
The 35Sulphate incorporation (35SO42− assay) was applied to tibial and patellar cartilage of wild‐type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4‐day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII‐deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro‐CT). Four‐ and 16‐day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the 35SO42− assay, with the contralateral knee as control.
Results
In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood‐exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood‐exposed knee.
Conclusion
For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the 35SO42− assay in a haemophilic rat model, establishing this assay as a novel method to study blood‐induced cartilage damage.</description><identifier>ISSN: 1351-8216</identifier><identifier>EISSN: 1365-2516</identifier><identifier>DOI: 10.1111/hae.13969</identifier><identifier>PMID: 32212362</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Animals ; arthropathies ; Blood ; Cartilage ; Cartilage, Articular - physiopathology ; Degeneration ; Disease Models, Animal ; experimental animal models ; haemarthrosis ; haemophilia ; Hemophilia A - complications ; Humans ; Knee ; Male ; Original ; Proteoglycans ; Proteoglycans - chemical synthesis ; Rats</subject><ispartof>Haemophilia : the official journal of the World Federation of Hemophilia, 2020-05, Vol.26 (3), p.e88-e96</ispartof><rights>2020 The Authors. published by John Wiley & Sons Ltd</rights><rights>2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5099-34563e00848c754dae75fa1a886c6809e12025b05710d7ed08677c633a0a26a53</citedby><cites>FETCH-LOGICAL-c5099-34563e00848c754dae75fa1a886c6809e12025b05710d7ed08677c633a0a26a53</cites><orcidid>0000-0001-8464-4775 ; 0000-0003-3242-5524 ; 0000-0002-2762-6033 ; 0000-0002-6701-2087</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhae.13969$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhae.13969$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32212362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pulles, Astrid E.</creatorcontrib><creatorcontrib>Vøls, Kåre K.</creatorcontrib><creatorcontrib>Christensen, Kristine R.</creatorcontrib><creatorcontrib>Coeleveld, Katja</creatorcontrib><creatorcontrib>Hansen, Axel K.</creatorcontrib><creatorcontrib>Vulpen, Lize F. D.</creatorcontrib><creatorcontrib>Petersen, Maj</creatorcontrib><creatorcontrib>Mastbergen, Simon C.</creatorcontrib><creatorcontrib>Roepstorff, Kirstine</creatorcontrib><creatorcontrib>Schutgens, Roger E. G.</creatorcontrib><creatorcontrib>Kjelgaard‐Hansen, Mads</creatorcontrib><creatorcontrib>Lafeber, Floris P. J. G.</creatorcontrib><title>Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats</title><title>Haemophilia : the official journal of the World Federation of Hemophilia</title><addtitle>Haemophilia</addtitle><description>Introduction
Haemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed.
Aim
To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage.
Methods
The 35Sulphate incorporation (35SO42− assay) was applied to tibial and patellar cartilage of wild‐type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4‐day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII‐deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro‐CT). Four‐ and 16‐day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the 35SO42− assay, with the contralateral knee as control.
Results
In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood‐exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood‐exposed knee.
Conclusion
For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the 35SO42− assay in a haemophilic rat model, establishing this assay as a novel method to study blood‐induced cartilage damage.</description><subject>Animal models</subject><subject>Animals</subject><subject>arthropathies</subject><subject>Blood</subject><subject>Cartilage</subject><subject>Cartilage, Articular - physiopathology</subject><subject>Degeneration</subject><subject>Disease Models, Animal</subject><subject>experimental animal models</subject><subject>haemarthrosis</subject><subject>haemophilia</subject><subject>Hemophilia A - complications</subject><subject>Humans</subject><subject>Knee</subject><subject>Male</subject><subject>Original</subject><subject>Proteoglycans</subject><subject>Proteoglycans - chemical synthesis</subject><subject>Rats</subject><issn>1351-8216</issn><issn>1365-2516</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kb9uFDEQh1cIRMJBwQsgSzRQbOI_Z6-3QYqiQJAiQQG1NWfP3Try2oe9G3QdLV2eMU-Cw4UoIOHGY_nTN2P_muYlo0esruMB8IiJXvWPmkMmlGy5ZOrxbS1ZqzlTB82zUi4pZYJT9bQ5EJwzLhQ_bH5-zmnCtAk7C5GUXZwGLL6QDBMSKARITFcYyIjTkByZUq2gzBnJKqTkbn5c--hmi45YyJMPsEHicIMRq8GnSHyshli5OuSYtoMP3hKIjjw8V7Y8b56sIRR8cbcvmq_vz76cnrcXnz58PD25aK2kfd-KpVQCKdVLbTu5dICdXAMDrZVVmvbIOOVyRWXHqOvQUa26ziohgAJXIMWiebf3bufViM5inDIEs81-hLwzCbz5-yb6wWzSlekE06I2XzRv7gQ5fZuxTGb0xWIIEDHNxXBRMS6pYBV9_Q96meYc6_MMX1LV6U5zXqm3e8rmVErG9f0wjJrbgE39K_M74Mq-ejj9Pfkn0Qoc74HvPuDu_yZzfnK2V_4CadOzcw</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Pulles, Astrid E.</creator><creator>Vøls, Kåre K.</creator><creator>Christensen, Kristine R.</creator><creator>Coeleveld, Katja</creator><creator>Hansen, Axel K.</creator><creator>Vulpen, Lize F. D.</creator><creator>Petersen, Maj</creator><creator>Mastbergen, Simon C.</creator><creator>Roepstorff, Kirstine</creator><creator>Schutgens, Roger E. G.</creator><creator>Kjelgaard‐Hansen, Mads</creator><creator>Lafeber, Floris P. J. G.</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8464-4775</orcidid><orcidid>https://orcid.org/0000-0003-3242-5524</orcidid><orcidid>https://orcid.org/0000-0002-2762-6033</orcidid><orcidid>https://orcid.org/0000-0002-6701-2087</orcidid></search><sort><creationdate>202005</creationdate><title>Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats</title><author>Pulles, Astrid E. ; Vøls, Kåre K. ; Christensen, Kristine R. ; Coeleveld, Katja ; Hansen, Axel K. ; Vulpen, Lize F. D. ; Petersen, Maj ; Mastbergen, Simon C. ; Roepstorff, Kirstine ; Schutgens, Roger E. G. ; Kjelgaard‐Hansen, Mads ; Lafeber, Floris P. J. G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5099-34563e00848c754dae75fa1a886c6809e12025b05710d7ed08677c633a0a26a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>arthropathies</topic><topic>Blood</topic><topic>Cartilage</topic><topic>Cartilage, Articular - physiopathology</topic><topic>Degeneration</topic><topic>Disease Models, Animal</topic><topic>experimental animal models</topic><topic>haemarthrosis</topic><topic>haemophilia</topic><topic>Hemophilia A - complications</topic><topic>Humans</topic><topic>Knee</topic><topic>Male</topic><topic>Original</topic><topic>Proteoglycans</topic><topic>Proteoglycans - chemical synthesis</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pulles, Astrid E.</creatorcontrib><creatorcontrib>Vøls, Kåre K.</creatorcontrib><creatorcontrib>Christensen, Kristine R.</creatorcontrib><creatorcontrib>Coeleveld, Katja</creatorcontrib><creatorcontrib>Hansen, Axel K.</creatorcontrib><creatorcontrib>Vulpen, Lize F. D.</creatorcontrib><creatorcontrib>Petersen, Maj</creatorcontrib><creatorcontrib>Mastbergen, Simon C.</creatorcontrib><creatorcontrib>Roepstorff, Kirstine</creatorcontrib><creatorcontrib>Schutgens, Roger E. G.</creatorcontrib><creatorcontrib>Kjelgaard‐Hansen, Mads</creatorcontrib><creatorcontrib>Lafeber, Floris P. J. G.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pulles, Astrid E.</au><au>Vøls, Kåre K.</au><au>Christensen, Kristine R.</au><au>Coeleveld, Katja</au><au>Hansen, Axel K.</au><au>Vulpen, Lize F. D.</au><au>Petersen, Maj</au><au>Mastbergen, Simon C.</au><au>Roepstorff, Kirstine</au><au>Schutgens, Roger E. G.</au><au>Kjelgaard‐Hansen, Mads</au><au>Lafeber, Floris P. J. G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats</atitle><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle><addtitle>Haemophilia</addtitle><date>2020-05</date><risdate>2020</risdate><volume>26</volume><issue>3</issue><spage>e88</spage><epage>e96</epage><pages>e88-e96</pages><issn>1351-8216</issn><eissn>1365-2516</eissn><abstract>Introduction
Haemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed.
Aim
To develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage.
Methods
The 35Sulphate incorporation (35SO42− assay) was applied to tibial and patellar cartilage of wild‐type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4‐day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII‐deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro‐CT). Four‐ and 16‐day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the 35SO42− assay, with the contralateral knee as control.
Results
In vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood‐exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood‐exposed knee.
Conclusion
For the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the 35SO42− assay in a haemophilic rat model, establishing this assay as a novel method to study blood‐induced cartilage damage.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32212362</pmid><doi>10.1111/hae.13969</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8464-4775</orcidid><orcidid>https://orcid.org/0000-0003-3242-5524</orcidid><orcidid>https://orcid.org/0000-0002-2762-6033</orcidid><orcidid>https://orcid.org/0000-0002-6701-2087</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animal models Animals arthropathies Blood Cartilage Cartilage, Articular - physiopathology Degeneration Disease Models, Animal experimental animal models haemarthrosis haemophilia Hemophilia A - complications Humans Knee Male Original Proteoglycans Proteoglycans - chemical synthesis Rats |
| title | Proteoglycan synthesis rate as a novel method to measure blood‐induced cartilage degeneration in non‐haemophilic and haemophilic rats |
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