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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Aged, Aged, 80 and over, Apoptosis, Cartilage, Articular, Chondrocytes, Dinoprostone, Female, Humans, Interleukin-1beta, Lamin Type A, Male, Middle Aged, Osteoarthritis, Knee.
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Does perturbation of nuclear lamin A cause cell death in chondrocytes? Context: 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. 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. 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-1β 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.
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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. Final Decision: yes