title: Estrogen reduces cellular aging in human mesenchymal stem cells and chondrocytes.
abstract: 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 17β-estradiol (E(2)) significantly decelerated telomere attrition in MSCs and chondrocytes while postmenopausal E(2) concentration had no significant effects. The estrogen agonist-antagonist tamoxifen 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 β-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.
authors.affiliation: Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Breu
authors.forename: Benedikt
authors.initials: B
authors.lastname: Sprinzing
authors.forename: Katharina
authors.initials: K
authors.lastname: Merkl
authors.forename: Volker
authors.initials: V
authors.lastname: Bechmann
authors.forename: Richard
authors.initials: R
authors.lastname: Kujat
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Jenei-Lanzl
authors.forename: Lukas
authors.initials: L
authors.lastname: Prantl
authors.forename: Peter
authors.initials: P
authors.lastname: Angele
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D004958:Estradiol / Q000502:physiology*; D006801:Humans; D008297:Male; D008593:Menopause / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D016615:Telomere / Q000502:physiology*
chemical_list: D004958:Estradiol