RESSALVA 

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somente a partir de 28/04/2024. 



UNIVERSIDADE ESTADUAL PAULISTA

“JÚLIO DE MESQUITA FILHO”

FACULDADE DE MEDICINA VETERINÁRIA E ZOOTECNIA

BOTUCATU

AVALIAÇÃO DE BIOMARCADORES NO LÍQUIDO SINOVIAL EM
EQUINOS COM SINOVITE INDUZIDA TRATADOS COM CÉLULAS-

TRONCO MESENQUIMAIS

VITTORIA GUERRA ALTHEMAN

Botucatu, São Paulo

Abril de 2022.



UNIVERSIDADE ESTADUAL PAULISTA

“JÚLIO DE MESQUITA FILHO”

FACULDADE DE MEDICINA VETERINÁRIA E ZOOTECNIA

AVALIAÇÃO DE BIOMARCADORES NO LÍQUIDO SINOVIAL EM
EQUINOS COM SINOVITE INDUZIDA TRATADOS COM CÉLULAS-

TRONCO MESENQUIMAIS

VITTORIA GUERRA ALTHEMAN

Dissertação apresentada junto
ao Programa de Biotecnologia
da Animal para obtenção do
Título de Mestre. Universidade
Estadual Paulista “Júlio de
Mesquita Filho” Faculdade de
Medicina Veterinária e
Zootecnia

Orientadora: Profª Dra. Ana Liz Garcia Alves

Botucatu, São Paulo

Abril de 2022

Autor: Vittoria Guerra Altheman

Data: 28 de Abril de 2022.



FICHA CATALOGRÁFICA ELABORADA PELA SEÇÃO TÉC. AQUIS. TRATAMENTO DA INFORM.

DIVISÃO TÉCNICA DE BIBLIOTECA E DOCUMENTAÇÃO - CÂMPUS DE BOTUCATU - UNESP

BIBLIOTECÁRIA RESPONSÁVEL: ROSEMEIRE APARECIDA VICENTE-CRB 8/5651



iii

Comissão Examinadora

Profª Dra. Ana Liz Garcia Alves

Orientadora

Departamento de Cirurgia Veterinária e Reprodução Animal

FMVZ, UNESP, Botucatu

Profª Dra. Fernanda de Castro Stievani

Membro

Departamento de Ciências Agrárias. Universidade de Taubaté

Medicina Veterinária, UNITAU, Taubaté

Prof. Dr. Marcos Jun Watanabe

Membro

Departamento de Cirurgia Veterinária e Reprodução Animal

FMVZ, UNESP, Botucatu



iii

Agradecimentos

Agradeço à Profª Dra. Ana Liz Garcia Alves por me orientar desde o início e por

compartilhar seus conhecimentos, sabedoria e conselhos.

A todos que me acompanharam em cada processo da minha formação como pessoa,

desde a infância até agora: minha família de sangue, minha família de Botucatu, meus

amigos e colegas.

À CAPES, à CNPq e à FAPESP pela concessão da bolsa de mestrado. O presente

trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de

Nível Superior - Brasil (CAPES) - Código de Financiamento 001, pelo Programa de

Demanda Social.



iv

LISTA DE FIGURAS

Figura 1. Mecanismos da progressão da osteoartrite. 6

Figura 2. Análise da concentração do marcador CPII do líquido sinovial no
momento inicial, 8, 24, 72 horas, 7 e 14 dias após a indução da sinovite. Os
tratamentos foram realizados após a coleta do
momento 8h 28

Figura 3. Análise da concentração sinovial do marcador C2C no momento inicial,
8, 24, 72 horas, 7 e 14 dias após a indução da
sinovite 29

Figura 4. Análise da concentração sinovial do marcador CS846 no momento
inicial, 8, 24, 72 horas, 7 e 14 dias após a indução da
sinovite 31



v

LISTA DE TABELAS

Tabela 1 . Quantificação da concentração sinovial de CPII. As letras minúsculas
indicam comparação do mesmo grupo nos diferentes momentos e as maiúsculas
comparam os diferentes grupos no mesmo momento 29

Tabela 2. Quantificação da concentração sinovial de C2C. As letras minúsculas
indicam comparação do mesmo grupo nos diferentes momentos e as maiúsculas
comparam os diferentes grupos no mesmo momento 30

Tabela 3. Quantificação da concentração sinovial de CS846. As letras minúsculas
indicam comparação do mesmo grupo nos diferentes momentos e as maiúsculas
comparam os diferentes grupos no mesmo momento 31



vi

SUMÁRIO

RESUMO vii
ABSTRACT viii
Capítulo 1 1

1. Introdução e Justificativa 1

2. Revisão bibliográfica 3
3. Referências 11

Capítulo 2 19
1. INTRODUÇÃO 21
2. MATERIAL E MÉTODOS 22
2.1. Delineamento experimental 22
2.2. Obtenção e Cultivo das CTMs 25
2.3. Indução experimental da sinovite e tratamento 26
2.4. Quantificação de C2C, CPII e CS846 por ELISA 26
2.5. Análise estatística 27
3. RESULTADOS 28
3.1. Concentração sinovial de CPII 28
3.2. Concentração sinovial de C2C 29
3.3. Concentração sinovial de CS846 30
4. DISCUSSÃO 32

5. CONCLUSÃO 37
6. REFERÊNCIAS 39



vii

ALTHEMAN, V. G. Avaliação de biomarcadores no líquido sinovial em equinos com
sinovite induzida tratados com células-tronco mesenquimais. Botucatu, 2022. Dissertação
de Mestrado. 42 páginas. Faculdade de Medicina Veterinária e Zootecnia, câmpus
Botucatu, Universidade Estadual Paulista “Júlio de Mesquita Filho”.

RESUMO

Os constantes impactos no sistema locomotor de equinos atletas gerados pelo intenso

exercício físico levam ao surgimento de lesões articulares, como a inflamação da

membrana sinovial que, se não tratada, pode evoluir para um quadro de osteoartrite (OA)

e posterior afastamento do esporte. A utilização de células tronco mesenquimais (CTMs)

vem ganhando destaque nestes casos como uma possibilidade de tratamento que busca

modificar a progressão desta enfermidade. O objetivo do presente trabalho foi investigar o

efeito das CTMs alogênicas derivadas da membrana sinovial (CTMms) sobre a síntese e

degradação da cartilagem articular em casos de sinovite aguda em equinos. A sinovite foi

induzida utilizando 0,5ng de LPS via intra-articular (IA) e os animais foram tratados 8

horas após a indução. O grupo controle recebeu como tratamento 2 mL de PBS IA,

enquanto o grupo tratado recebeu 107 CTMms IA. Foi realizada a determinação da

concentração sinovial dos biomarcadores de síntese e degradação de colágeno, CPII e

C2C respectivamente, e de síntese de agrecam, CS846, através de teste

imunoenzimático (ELISA). A análise revelou aumento significativo nos níveis de CPII (P=

0,019) e de CS846 (P=0,032) no grupo controle no momento 14 dias e também aumento

nos níveis de C2C (P= 0,015) no momento 24h, quando comparados com o grupo tratado.

Os dados avaliados sugerem que as CTMs interagiram na manutenção da homeostase da

cartilagem articular, exercendo uma atividade no ambiente que resultou em menor dano

nas primeiras 24 horas e, consequentemente, menor necessidade de reparo posterior.

Palavras-chave: terapia regenerativa; membrana sinovial; inflamação sinovial.



viii

ALTHEMAN, V. G. Evaluation of biomarkers in synovial fluid in horses with induced

synovitis treated with mesenchymal stem cells. Botucatu, 2022. Master 's Thesis. 42

pages. School of Veterinary Medicine and Animal Science, campus Botucatu , São Paulo

State University “Júlio de Mesquita Filho”.

ABSTRACT

The constant impacts on the locomotor system of equine athletes generated by intense

physical exercise lead to the emergence of joint injuries, such as inflammation of the

synovial membrane that, if left untreated, can progress to osteoarthritis (OA) and

subsequent withdrawal from sport. The use of mesenchymal stem cells (MSCs) has been

gaining prominence in these cases as a possible treatment that seeks to modify the

progression of this disease. The aim of the present work was to investigate the effect of

allogeneic MSCs derived from the synovial membrane (mMSCs) on the synthesis and

degradation of articular cartilage in cases of acute synovitis in horses. Synovitis was

induced using 0.5ng of LPS via intra-articular (IA) and the animals were treated 8 hours

after induction. The control group received 2 mL of PBS IA as treatment, while the treated

group received 107 mMSCs IA. The synovial concentration of collagen synthesis and

degradation biomarkers, CPII and C2C, respectively, and aggrecan synthesis biomarkers,

CS846, were determined by enzyme immunoassay (ELISA). The analysis revealed a

significant increase in the levels of CPII (P=0.019) and CS846 (P=0.032) in the control

group at 14 days and also an increase in C2C levels (P=0.015) at 24h, when compared

with the group treated. The evaluated data suggest that MSCs interacted in the

maintenance of articular cartilage homeostasis, exerting an activity in the environment that

resulted in less damage in the first 24 hours and, consequently, less need for later repair.

Keywords: regenerative therapy; synovial membrane; synovial inflammation.



12

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43

Agradecimentos

À CAPES, à CNPq e à FAPESP pela concessão da bolsa de mestrado. O presente

trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de

Nível Superior - Brasil (CAPES) - Código de Financiamento 001, pelo Programa de

Demanda Social.



44

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