Histone deacetylase inhibitors suppress interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes

Abstract

These data indicate that HDAC inhibitors suppressed IL-1-induced NO and PGE(2) synthesis, iNOS and COX-2 expression, as well as proteoglycan degradation. The suppressive effect of HDAC inhibitors is not due to impaired DNA-binding activity of NF-kappaB. These findings also suggest that HDAC inhibitors may be of potential therapeutic value in the treatment of OA.

Switching gears to an arthritis gene expression network by SirT1 cleavage

“…In fact, combinatorial transcriptional protein complex formation is considered the basis of spatiotemporal gene regulation (3)(4)(5)(6)(7). Consistent with this, SOX9 associates with cofactors that regulate histone acetylation and deacetylation, which in turn impact the SOX9-dependent transcriptional program (3)(4)(5)(6)(7).…”

“…In general, transcription factors may require transcription cofactors that regulate chromatin via histone modification (e.g., acetylation or methylation) (3)(4)(5)(6)(7). In fact, combinatorial transcriptional protein complex formation is considered the basis of spatiotemporal gene regulation (3)(4)(5)(6)(7). Consistent with this, SOX9 associates with cofactors that regulate histone acetylation and deacetylation, which in turn impact the SOX9-dependent transcriptional program (3)(4)(5)(6)(7).…”

“…While the transcription targets of SOX9 during development and homeostasis have not been fully determined, it is well established that the transcription of cartilage-specific extracellular matrix genes, such as COL2A1, are directly and tightly regulated by SOX9 (1-3). In general, transcription factors may require transcription cofactors that regulate chromatin via histone modification (e.g., acetylation or methylation) (3)(4)(5)(6)(7). In fact, combinatorial transcriptional protein complex formation is considered the basis of spatiotemporal gene regulation (3)(4)(5)(6)(7).…”

“…While SOX9 does not have intrinsic acetylase activity, the various protein complexes that associate with SOX9 provide it with the ability to fine tune the transcription of its target genes (4)(5)(6)(7). This complex formation is tightly regulated by cellular signals and may act as a sensor for cellular status and developmental timing, and it orchestrates the SOX9 gene expression network.…”

“…Deacetylation generally terminates or represses gene expression (7,8). Two families of histone deacetylases (HDAs) exist: the classic HDA family and the NADϩ-dependent SIR2 family (also known as class III HDAs).…”