ment with all 4 HDIs, consistent with effective suppression of HDAC activity. The most effective specific HDI was MS275, which showed similar A-H3 levels to TSA, but exhibited some undesirable effects of pan-HDI. PCI increased A-H3 levels, though not as effective as MS275, but also reduced the negative effects of TSA, such as decreased COX-2 and MMP-3 expression under treatment with IL1b. Also, the additive effect of TSA and IL1b on the secretion of MMP3was not observed in the case of PCI. Chondrocyte proliferation and survival was unaffected by the tested HDIs after 24 h of culture, with the exception of Droxinostat at concentration over 20 mm(decreased proliferation as shown by MTS assay and increased cell death as shown by Live/Dead assay). However, upon longer incubation (48 h), both TSA (200 nM) and Droxinostat reduced chondrocyte proliferation, while MS275, PCI and Tubostatin A increased it. Conclusions: The HDI, PCI, appears to be a promising candidate for reducing inflammatory and catabolic markers in chondrocytes exposed to pro-inflammatory cytokines. Further studies will investigate the effect of increasing PCI concentrations in two in vitro chondrocytebased OA models: (1) IL1b treatment; and (2) exposure to supraphysiological mechanical loading. In addition, MS275 could be a good alternative to pan-HDAC inhibitors, such as TSA, when longer exposure times are needed. Grant support: Arthritis Foundation, Commonwealth of PA, Dept of Health.