Regulation of type II collagen expression by histone deacetylase in articular chondrocytes.
Histone deacetylase (HDAC) regulates various cellular processes by modulating gene expression. Here, we investigated the role of HDAC in the expression of type II collagen, a marker of differentiated chondrocytes. We found that HDAC activity in primary articular chondrocytes decreases during dedifferentiation induced by serial monolayer culture and that the activity recovered during redifferentiation induced by three-dimensional culture in a cell pellet. Inhibition of HDAC with trichostatin A or PXD101 was sufficient to block type II collagen expression in primary culture chondrocytes. HDAC inhibition also blocked the redifferentiation of dedifferentiated chondrocytes by suppressing the synthesis and accumulation of type II collagen. HDAC inhibition promoted the expression of Wnt-5a, which is known to inhibit type II collagen expression, and knockdown of Wnt-5a blocked the ability of HDAC inhibitors to suppress type II collagen expression. In addition, the induction of Wnt-5a expression by HDAC inhibitors was associated with acetylation of the Wnt-5a promoter. Taken together, our results suggest that HDAC promotes type II collagen expression by suppressing the transcription of Wnt-5a.
Huh
Yun Hyun
YH
Department of Life Sciences, Research Center for Biomolecular Nanotechnology, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
Ryu
Je-Hwang
JH
Chun
Jang-Soo
JS
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000201:enzymology / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D017077:Culture Media, Conditioned; D017931:DNA Primers; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D011817:Rabbits
D024043:Collagen Type II; D017077:Culture Media, Conditioned; D017931:DNA Primers; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases