Set7/9 represses SirT1 to induce collagen type II expression in 3D cultured human chodrocytes
Abstract
s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S170 324 SET7/9 REPRESSES SIRT1 TO INDUCE COLLAGEN TYPE II EXPRESSION IN 3D CULTURED HUMAN CHODROCYTES H. Oppenheimer y, H. Meir y, A. Zini z, A. Haze z, L. Kandel z, Y. Mattan z, M. Leibergall z, M. Dvir-Ginzberg y. yHebrew Univ. of Jerusalem, Jerusalem, Israel; zHebrew Univ. of Jerusalem-Hadassah Med. Center, Jerusalem, Israel Abstract Objective: Collagen type II (Col-II) plays a significant role in skeletalObjective: Collagen type II (Col-II) plays a significant role in skeletal development and cartilage homeostasis and its loss with age is associated with degenerative joint diseases such as osteoarthritis (OA). Previously findings establish that the protein deacetylase SirT1 is required for enhanced expression of Col-IIa1, a major cartilage structural component of Col-II. Here we profile the mechanism by which SirT1 activates promoter-driven Col-IIa1 expression. Methods: Chondrocytes derived from human osteoarthritic knee joints were encapsulated in three-dimensional alginate hydrogel microbeads (3D) and compared to paired monolayer (2D, passage 2) cultures derived from the same donor tissue. 3D-cultured cells displayed augmented expression of Col-IIa1 and were subject to serial chromatin immunoprecipitation (ChIP) and ChIP reChIP analyses to characterize epigenetic variations as compared to 2D cultures. Results: ChIP analyses exhibited enrichment for SirT1 and the histone methyl transferase Set7/9, which formed a…
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