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Doctoral Thesis
DOI
https://doi.org/10.11606/T.58.2020.tde-04102022-084623
Document
Author
Full name
Thaís Aparecida Xavier
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Alves, Sandra Yasuyo Fukada (President)
Daldegan, Andiara De Rossi
Lima, Vilma de
Silva, Marcelo José Barbosa
Title in Portuguese
Monócitos provenientes de indivíduos obesos se diferenciam em osteoclastos maiores e com menor expressão do receptor CMKLR1 in vitro
Keywords in Portuguese
CMKLR1
Obesidade
Osteoclastogênese
Quemerina
Abstract in Portuguese
A obesidade é uma doença representada por aumento excessivo de tecido adiposo e que constitui fator de risco para diversas patologias. A respeito da saúde óssea, trabalhos prévios sugerem que a obesidade pode exercer efeito tanto protetor quanto negativo à microarquitetura dos ossos. A quemerina, uma citocina produzida pelo tecido adiposo, pode ser a ligação entre obesidade e o metabolismo ósseo alterado. O objetivo desta pesquisa foi avaliar a osteoclastogênese de monócitos de indivíduos obesos e controles, in vitro, bem como o efeito da quemerina sobre esse processo. Para isso, para os grupos analisados (obesidade, n=10, e controle, n=10), foram dosadas as concentrações séricas de quemererina e realizadas culturas com os monócitos CD14+ estimulados com M-CSF e RANKL para induzir a diferenciação de osteoclastos. Uma parte das amostras celulares foi ainda exposta à quemerina e, após a diferenciação celular, avaliaram-se número e área de osteoclastos formados. Foi também avaliada a expressão relativa de genes associados à diferenciação e atividade celular, NFATc1 e CTSK, e dos receptores da quemerina, CMKLR1, CCRL2 e GPR1. Os resultados demonstraram haver maior concentração sérica de quemerina no grupo obesidade (p<0,05). Nos experimentos in vitro, houve um número menor de osteoclastos formados no grupo obesidade (p<0,05, com e sem adição de quemerina), sem diferença estatisticamente significante quanto à área de osteoclastos formados. Verificou-se que as expressões de NFATc1 e CTSK não foram alteradas em indivíduos obesos ou com a exposição à quemerina. No grupo obesidade, observou-se uma menor expressão relativa do gene CMKLR1 (p<0,05, com e sem adição de quemerina), enquanto a expressão do CCRL2 foi semelhante entre os grupos e do GPR1 não foi detectada em nenhuma das amostras. Com base nos dados deste estudo, conclui-se que, além de apresentarem maior exposição sistêmica à quemerina, indivíduos obesos podem apresentar diferenciação de osteoclastos maiores e menor expressão do gene CMKLR1 em comparação a indivíduos controles.
Title in English
Monocytes from obese individuals differentiate into larger osteoclasts and have lower CMKLR1 receptor expression in vitro
Keywords in English
Chemerin
CMKLR1
Obesity
Osteoclastogenesis
Abstract in English
Obesity is a complex disease involving excess of adipose tissue and constitutes a risk factor for several pathologies. Regarding bone health, previous work suggests that obesity may have both protective and negative effects on bone microarchitecture. Chemerin, a cytokine produced by adipose tissue, may be the link between obesity and altered bone metabolism. The objective of this research was to evaluate the osteoclastogenesis of cells from obese and control individuals, in vitro, as well as the effect of the chemerin on this process. For this, for both groups (obesity, n=10, and control, n=10), the serum concentration of chemerin was measured, and CD14+ monocytes were cultured and osteoclasts differentiation was induced by M-CSF and RANKL. The culture was also exposed to chemerin and, after cell differentiation, the number and area of osteoclasts formed were evaluated. The relative expression of genes associated with osteoclasts differentiation and activity (NFATc1 and CTSK) and chemerin receptors (CMKLR1, CCRL2 and GPR1) were also evaluated. The results showed higher serum concentration of chemerin in the obesity group (p<0,05). In the in vitro experiments, there was a smaller number of osteoclasts formed in the obesity group (p<0,05, with and without the addition of chemerin). The results show that obesity or chemerin had no effect on the area of osteoclasts formed. The expression of NFATc1 and CTSK were not altered in osteoclasts from obese individuals or those with chemerin exposure. In the obesity group, a lower expression of the CMKLR1 gene was observed (p <0,05, with and without the addition of chemerin) while the expression of CCRL2 were similar between groups. The expression of GPR1 gene was not detected in any sample. Based on the data from this study, it can be concluded that, in addition to present higher systemic exposure to chemerin, obese individuals may exhibit differentiation of larger osteoclasts and lower expression of the CMKLR1 gene compared to control individuals.
 
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Publishing Date
2022-10-05
 
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