Estrogen Reduces Cellular Aging in Human Mesenchymal Stem Cells and Chondrocytes

Chondrocyte aging is associated with cartilage degeneration and senescence impairs the regenerative potential of mesenchymal stem cells (MSCs). Estrogen exerts profound effects on human physiology including articular cartilage and MSCs. The present study should analyze the effects of pre- and postmenopausal estrogen concentrations on chondrogenic cells. Physiologic premenopausal concentrations of 17 beta-estradiol (E-2) significantly decelerated telomere attrition in MSCs and chondrocytes while postmenopausal E-2 concentration had no significant effects. The estrogen agonist antagonist tainoxifen did not affect telomere biology, but inhibited the E-2-stimulated reduction in telomere shortening. E-2 and tamoxifen did not influence cell proliferation, cell morphology, and beta-galactosidase staining in chondrogenic cells. E-2 treatment did not affect the telomere-associated proteins TRF1 and TRF2. E-2 had no regulatory effects on the expression rates of the cell cycle regulator p21 and the DNA repair proteins SIRT1 and XRCC5. In spite of reducing telomere shortening in aging MSCs and chondrocytes, estrogen is not able to prevent somatic cells from replicative exhaustion and from finally entering senescence. The fade of telomere shortening under pre- to postmenopausal estrogen concentrations suggests, at least in part, a senescence-dependent cause for the onset of osteoarthritis in women after menopause. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:1563-1571, 2011