Perturbation of nuclear lamin A causes cell death in chondrocytes

Arthritis Rheum. 2012 Jun;64(6):1940-9. doi: 10.1002/art.34360. Epub 2012 Jan 9.


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-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.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Dinoprostone / pharmacology
  • Female
  • Humans
  • Interleukin-1beta / pharmacology
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / genetics
  • Osteoarthritis, Knee / metabolism*


  • Interleukin-1beta
  • Lamin Type A
  • Dinoprostone