RESUMO
OBJECTIVE: The aim of this study is to determine the role of cytosine-adenine (CA) micro-satellite repeat sequence of ADAMTS9 gene on the development and progression of osteoarthritis (OA). METHODS: A total of 110 participants, including those with primary knee OA and healthy controls were enrolled in the study. Patients were stratified into two groups using the Kellgren-Lawrence staging (K-L staging) as group 1 for controls and mild OA and group 2 for moderate and severe OA. Genetic analyses were performed to determine the CA repeat length in ADAMTS9 gene. RESULTS: Twenty CA repeats were found to be statistically significant for differentiating groups 1 and 2 (P = 0.020). Age was the most significant risk factor involved, followed by ≥ 20 CA repeats and body mass index (P < 0.05). CA repeat length of ≥ 20 showed a 6.1-fold increase in probability for having OA at stage 3 or 4 compared to those of CA repeat length of < 20 (P = 0.004). In conclusion, the CA repeat length of ≥ 20 has a six-fold increase in probability for having severe OA. CONCLUSION: ADAMTS9 gene CA repeat polymorphism may be used to determine the prognosis for OA radiologic progression. Being the first in the literature reporting the CA repeat in the promotor region of ADAMTS9 gene in patients with OA, our study could be highlighted further in future research with larger sample size.
Assuntos
Proteína ADAMTS9/genética , Repetições de Microssatélites , Osteoartrite do Joelho/genética , Polimorfismo Genético , Adenina , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Citosina , Progressão da Doença , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/enzimologia , Fenótipo , Prognóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
PURPOSE: The purpose of this study was to determine the effects of hypericin on MCF-7 (Michigan Cancer Foundation- 7) breast cancer cells, as it is known to exert an antitumor effect on the expression and regulation of ADAMTS1, 3, 10 and the p53 gene in breast cancer cells. METHODS: MFC-7 cells were cultured and subjected separately to various doses (1, 5 and 7.5 µg /mL) hypericin. After 24 hrs, RNA was isolated and transcribed into cDNA. Expression analysis was performed by real time (RT)-PCR and cell survival was determined by the XTT assay. RESULTS: While the expression of ADAMTS1 in MFC-7 cells decreased to 0.04-fold after exposure to 1 µg /mL hypericin, the expression increased by 5.6- and 36-fold with 5 and 7.5 µg/mL, respectively. Furthermore, ADAMTS3 expression in MCF7 cells increased 3.9-fold with the use of 5 µg /mL of hypericin. These concentrations of hypericin did not lead to significant changes in the expression of ADAMTS10 and the p53 gene. Viability of cancer cells as evaluated by the XTT assay showed that hypericin concentration of 7.5 µg /mL led to increased apoptosis of cancer cells. CONCLUSION: The increase in ADAMTS1 expression may prevent metastasis or facilitate the development of an adjuvant factor with tumor-suppressive effects. Hypericin may therefore exert its antitumor and apoptotic effects in MFC-7 cells via ADAMTS1 and ADAMTS3.