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Perturbation of nuclear lamin A causes cell death in chondrocytes.
Attur, Mukundan; Ben-Artzi, Ami; Yang, Qing; Al-Mussawir, Hayf E; Worman, Howard J; Palmer, Glyn; Abramson, Steven B.
Afiliação
  • Attur M; New York University School of Medicine, New York, NY, USA.
Arthritis Rheum ; 64(6): 1940-9, 2012 Jun.
Article em En | MEDLINE | ID: mdl-22231515
OBJECTIVE: Mutations in LMNA encoding the A-type lamins cause several diseases, including those with features of premature aging and skeletal abnormalities. The aim of this study was to examine the expression of lamin A in cartilage from patients with osteoarthritis (OA) and the effects of its overexpression on chondrocyte senescence and apoptosis. METHODS: Human chondrocyte-like cells (SW-1353) were used. RNA isolated from human OA and non-OA cartilage was used for profiling messenger RNA expression, using Affymetrix microarray analysis. The effects of lamin A overexpression on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, and cytochrome c release, and with a TUNEL assay. Western blotting was performed to determine protein expression. RESULTS: Lamin A expression was markedly elevated in OA cartilage samples compared with non-OA control samples. Western blot analysis confirmed increased expression of lamin A in OA compared with non-OA cartilage. Interleukin-1ß treatment inhibited lamin A accumulation, whereas treatment with prostaglandin E(2) (PGE(2) ) caused a marked increase in lamin A accumulation. These effects of exogenous PGE(2) on lamin A expression were mediated via the EP(2) /EP(4) receptors. Transfected chondrocytes that expressed lamin A displayed markers of early senescence/apoptosis. CONCLUSION: The results of this study suggest that lamin A is up-regulated in OA chondrocytes, and that increased nuclear accumulation of lamin A in response to catabolic stress may account for the premature aging phenotype and apoptosis of OA chondrocytes.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cartilagem Articular / Apoptose / Condrócitos / Osteoartrite do Joelho / Lamina Tipo A Tipo de estudo: Etiology_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cartilagem Articular / Apoptose / Condrócitos / Osteoartrite do Joelho / Lamina Tipo A Tipo de estudo: Etiology_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2012 Tipo de documento: Article