Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos

Detalhes bibliográficos
Autor(a) principal: Franco, Renata Nogueron
Data de Publicação: 2011
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/5131
Resumo: Osteoarthritis (OA), a degenerative joint disease, is one of the most frequent causes of pain in the musculoskeletal system and of the inability to work in Brazil and the world. It is a multifactor, chronic disease, leading to progressive functional inability. It can arise as a result of injuries to structures such as the anterior crossed ligament and/or meniscus (post-traumatic OA), which, in this case, can affect individuals in any age range. The development of osteoarthritis includes multiple changes in the extracellular cartilage matrix, altering the normal morphological configuration of the joint involved, leading to a lack of equilibrium between the synthesis and degradation of products in this matrix. Although OA is not considered primordially as an inflammatory disease, inflammation of the joint has been shown to be a potential amplifier of the degenerative process. Thus the objective of the present study was to analyze potential biological markers in the serum and synovial fluid, and then correlate them with one another and with the morphological, inflammatory and functional alterations found in individuals with chronic injury of the anterior crossed ligament (ACL). The following techniques were used in the study: zymography, to determine the activity of the metallopeptidases 2 and 9 (MMP-2 and MMP-9); an immune-enzymatic assay (ELISA) to determine the presence of systemic and local cytokines; and a manual count of inflammatory cells (mononuclear and polymorphonuclear) by optical microscopy and spectrophotometry, in order to analyze for sulfated glycosaminoglycans (GAGs). The results indicated joint and systemic inflammation in chronic injury of the ACL by the detection of systemic and local cytokines, by the activity of MMP-9 and by the inflow of neutrophils. There were interactions between systemic and local cytokines, in which a cytokine did not always exert the same function in the serum as in the synovial fluid. The interleucines (IL) connected to degradation of the cartilage in chronic injury of the ACL were IL-12, IL-6 and IL-8, and those connected to pain and loss of function were IL-6 and IL-9. In counterpart, MMP-2 showed a negative correlation with the damage to the cartilage. It was concluded that the molecules studied had potential as biomarkers, since alterations were suggestive of injury and degradation of the cartilage. In addition, after the traumatic event resulting in rupture of the ACL, the ambient remained chronically inflamed and this inflammation was crucial for the high index of posttraumatic OA.
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spelling Franco, Renata NogueronRosa, Stela Márcia Mattiello Gonçalveshttp://lattes.cnpq.br/1406279816228350http://lattes.cnpq.br/7411522889447437cf6cb989-2357-4216-9ce8-cab44cd5c41b2016-06-02T20:18:15Z2011-11-242016-06-02T20:18:15Z2011-02-28FRANCO, Renata Nogueron. Biomarkers of cartilage metabolism and its relationship with morphological, inflammatory and functional changes: a study of secondary chondral injury in human knees. 2011. 109 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2011.https://repositorio.ufscar.br/handle/ufscar/5131Osteoarthritis (OA), a degenerative joint disease, is one of the most frequent causes of pain in the musculoskeletal system and of the inability to work in Brazil and the world. It is a multifactor, chronic disease, leading to progressive functional inability. It can arise as a result of injuries to structures such as the anterior crossed ligament and/or meniscus (post-traumatic OA), which, in this case, can affect individuals in any age range. The development of osteoarthritis includes multiple changes in the extracellular cartilage matrix, altering the normal morphological configuration of the joint involved, leading to a lack of equilibrium between the synthesis and degradation of products in this matrix. Although OA is not considered primordially as an inflammatory disease, inflammation of the joint has been shown to be a potential amplifier of the degenerative process. Thus the objective of the present study was to analyze potential biological markers in the serum and synovial fluid, and then correlate them with one another and with the morphological, inflammatory and functional alterations found in individuals with chronic injury of the anterior crossed ligament (ACL). The following techniques were used in the study: zymography, to determine the activity of the metallopeptidases 2 and 9 (MMP-2 and MMP-9); an immune-enzymatic assay (ELISA) to determine the presence of systemic and local cytokines; and a manual count of inflammatory cells (mononuclear and polymorphonuclear) by optical microscopy and spectrophotometry, in order to analyze for sulfated glycosaminoglycans (GAGs). The results indicated joint and systemic inflammation in chronic injury of the ACL by the detection of systemic and local cytokines, by the activity of MMP-9 and by the inflow of neutrophils. There were interactions between systemic and local cytokines, in which a cytokine did not always exert the same function in the serum as in the synovial fluid. The interleucines (IL) connected to degradation of the cartilage in chronic injury of the ACL were IL-12, IL-6 and IL-8, and those connected to pain and loss of function were IL-6 and IL-9. In counterpart, MMP-2 showed a negative correlation with the damage to the cartilage. It was concluded that the molecules studied had potential as biomarkers, since alterations were suggestive of injury and degradation of the cartilage. In addition, after the traumatic event resulting in rupture of the ACL, the ambient remained chronically inflamed and this inflammation was crucial for the high index of posttraumatic OA.A osteoartrite (OA), doença articular degenerativa, é uma das causas mais freqüentes de dor do sistema músculo-esquelético e de incapacidade para o trabalho no Brasil e no mundo. É uma doença crônica, multifatorial, que leva a uma incapacidade funcional progressiva. Pode surgir em decorrência de lesões em estruturas como ligamento cruzado anterior e/ou meniscos (OA pós-traumática), e neste caso, pode afetar indivíduos em qualquer faixa etária. O desenvolvimento da osteoartrite inclui múltiplas mudanças na matriz extracelular da cartilagem, o que altera a configuração morfológica normal da articulação envolvida, levando a um desequilíbrio entre a síntese e degradação dos produtos desta matriz. Apesar da OA não ser considerada primordialmente como uma doença inflamatória, a inflamação articular tem demonstrado um potencial amplificador do processo degenerativo. Sendo assim, o objetivo deste trabalho foi analisar potenciais marcadores biológicos no soro e no líquido sinovial, e em seguida correlacioná-los uns com os outros e com as alterações morfológicas, inflamatórias e funcionais encontradas em sujeitos com lesão crônica do ligamento cruzado anterior (LCA). Para este estudo foram utilizadas técnicas de: zimografia, para verificar a atividade das metalopeptidases 2 e 9 (MMP-2 e MMP-9); Ensaio imunoenzimático (ELISA), para constatar a presença das citocinas sistêmicas e locais; contagem manual de células inflamatórias (mononucleares e polimorfonucleares) por microscopia óptica e espectrofotometria para a análise dos glicosaminoglicanos sulfatados (GAGs). Os resultados apontaram para uma inflamação articular e sistêmica na lesão crônica do LCA, pela detecção de citocinas sistêmicas e locais, pela atividade das MMP-9 e pelo influxo de neutrófilos. Houve interações entre citocinas sistêmicas e locais, nas quais nem sempre uma citocina exerce a mesma função no soro e no líquido sinovial. As interleucinas (IL) ligadas à degradação da cartilagem na lesão crônica do LCA foram IL-12, IL-6 e IL-8 e as ligadas à dor e a perda de função foram IL-6 e IL-8. Em contrapartida, a MMP-2 apresentou correlação negativa com os danos na cartilagem. Conclui-se que, as moléculas estudadas apresentam potencial como biomarcadores, sendo suas alterações sugestivas de lesão e degradação da cartilagem. E ainda, que após o evento traumático responsável pelo rompimento do LCA, o ambiente permanece inflamado cronicamente e que esta inflamação é crucial para o alto índice de OA pós-traumática.application/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação em Fisioterapia - PPGFtUFSCarBROsteoartriteMarcadores biológicosCartilagem articularLigamento cruzado anteriorInflamaçãoFisioterapiaOsteoartrite pós-traumáticaLesão condralcitocinas, Células polimorfonucleares e mononuclearesGlicosaminoglicanosMetalopeptidasesPost-traumatic osteoarthritisChondral injuryCytokinesPolymorphonuclear and mononuclear cellsGlycosaminoglycansMetallopeptidasesCIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONALBiomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanosBiomarkers of cartilage metabolism and its relationship with morphological, inflammatory and functional changes: a study of secondary chondral injury in human kneesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-1-14f936219-f7d7-49fc-9dcc-ce3f39472005info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL3931.pdfapplication/pdf5591864https://repositorio.ufscar.br/bitstream/ufscar/5131/1/3931.pdfb4873ba462675328d3fc2005b8032afbMD51THUMBNAIL3931.pdf.jpg3931.pdf.jpgIM Thumbnailimage/jpeg8962https://repositorio.ufscar.br/bitstream/ufscar/5131/2/3931.pdf.jpg09cf55579772e3f505f37a59b8f68910MD52ufscar/51312023-09-18 18:31:05.525oai:repositorio.ufscar.br:ufscar/5131Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:05Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
dc.title.alternative.eng.fl_str_mv Biomarkers of cartilage metabolism and its relationship with morphological, inflammatory and functional changes: a study of secondary chondral injury in human knees
title Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
spellingShingle Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
Franco, Renata Nogueron
Osteoartrite
Marcadores biológicos
Cartilagem articular
Ligamento cruzado anterior
Inflamação
Fisioterapia
Osteoartrite pós-traumática
Lesão condral
citocinas, Células polimorfonucleares e mononucleares
Glicosaminoglicanos
Metalopeptidases
Post-traumatic osteoarthritis
Chondral injury
Cytokines
Polymorphonuclear and mononuclear cells
Glycosaminoglycans
Metallopeptidases
CIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONAL
title_short Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
title_full Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
title_fullStr Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
title_full_unstemmed Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
title_sort Biomarcadores do metabolismo da cartilagem e sua relação com as alterações morfológicas, inflamatórias e funcionais: um estudo sobre a lesão condral secundária em joelhos humanos
author Franco, Renata Nogueron
author_facet Franco, Renata Nogueron
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/7411522889447437
dc.contributor.author.fl_str_mv Franco, Renata Nogueron
dc.contributor.advisor1.fl_str_mv Rosa, Stela Márcia Mattiello Gonçalves
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1406279816228350
dc.contributor.authorID.fl_str_mv cf6cb989-2357-4216-9ce8-cab44cd5c41b
contributor_str_mv Rosa, Stela Márcia Mattiello Gonçalves
dc.subject.por.fl_str_mv Osteoartrite
Marcadores biológicos
Cartilagem articular
Ligamento cruzado anterior
Inflamação
Fisioterapia
Osteoartrite pós-traumática
Lesão condral
citocinas, Células polimorfonucleares e mononucleares
Glicosaminoglicanos
Metalopeptidases
topic Osteoartrite
Marcadores biológicos
Cartilagem articular
Ligamento cruzado anterior
Inflamação
Fisioterapia
Osteoartrite pós-traumática
Lesão condral
citocinas, Células polimorfonucleares e mononucleares
Glicosaminoglicanos
Metalopeptidases
Post-traumatic osteoarthritis
Chondral injury
Cytokines
Polymorphonuclear and mononuclear cells
Glycosaminoglycans
Metallopeptidases
CIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONAL
dc.subject.eng.fl_str_mv Post-traumatic osteoarthritis
Chondral injury
Cytokines
Polymorphonuclear and mononuclear cells
Glycosaminoglycans
Metallopeptidases
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FISIOTERAPIA E TERAPIA OCUPACIONAL
description Osteoarthritis (OA), a degenerative joint disease, is one of the most frequent causes of pain in the musculoskeletal system and of the inability to work in Brazil and the world. It is a multifactor, chronic disease, leading to progressive functional inability. It can arise as a result of injuries to structures such as the anterior crossed ligament and/or meniscus (post-traumatic OA), which, in this case, can affect individuals in any age range. The development of osteoarthritis includes multiple changes in the extracellular cartilage matrix, altering the normal morphological configuration of the joint involved, leading to a lack of equilibrium between the synthesis and degradation of products in this matrix. Although OA is not considered primordially as an inflammatory disease, inflammation of the joint has been shown to be a potential amplifier of the degenerative process. Thus the objective of the present study was to analyze potential biological markers in the serum and synovial fluid, and then correlate them with one another and with the morphological, inflammatory and functional alterations found in individuals with chronic injury of the anterior crossed ligament (ACL). The following techniques were used in the study: zymography, to determine the activity of the metallopeptidases 2 and 9 (MMP-2 and MMP-9); an immune-enzymatic assay (ELISA) to determine the presence of systemic and local cytokines; and a manual count of inflammatory cells (mononuclear and polymorphonuclear) by optical microscopy and spectrophotometry, in order to analyze for sulfated glycosaminoglycans (GAGs). The results indicated joint and systemic inflammation in chronic injury of the ACL by the detection of systemic and local cytokines, by the activity of MMP-9 and by the inflow of neutrophils. There were interactions between systemic and local cytokines, in which a cytokine did not always exert the same function in the serum as in the synovial fluid. The interleucines (IL) connected to degradation of the cartilage in chronic injury of the ACL were IL-12, IL-6 and IL-8, and those connected to pain and loss of function were IL-6 and IL-9. In counterpart, MMP-2 showed a negative correlation with the damage to the cartilage. It was concluded that the molecules studied had potential as biomarkers, since alterations were suggestive of injury and degradation of the cartilage. In addition, after the traumatic event resulting in rupture of the ACL, the ambient remained chronically inflamed and this inflammation was crucial for the high index of posttraumatic OA.
publishDate 2011
dc.date.available.fl_str_mv 2011-11-24
2016-06-02T20:18:15Z
dc.date.issued.fl_str_mv 2011-02-28
dc.date.accessioned.fl_str_mv 2016-06-02T20:18:15Z
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dc.identifier.citation.fl_str_mv FRANCO, Renata Nogueron. Biomarkers of cartilage metabolism and its relationship with morphological, inflammatory and functional changes: a study of secondary chondral injury in human knees. 2011. 109 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2011.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/5131
identifier_str_mv FRANCO, Renata Nogueron. Biomarkers of cartilage metabolism and its relationship with morphological, inflammatory and functional changes: a study of secondary chondral injury in human knees. 2011. 109 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2011.
url https://repositorio.ufscar.br/handle/ufscar/5131
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