Inhibition of histone deacetylase 6 by Tubastatin A attenuates the progress of osteoarthritis via improving mitochondrial function.

Inhibition of histone deacetylase 6 by Tubastatin A attenuates the progress of osteoarthritis via improving mitochondrial function. Am J Pathol. 2020 Sep 11;: Authors: Zheng Y, Chen Y, Lu X, Weng Q, Dai G, Yu Y, Yu K, Gao W Abstract As the only resident cell in articular cartilage, the steady state of chondrocytes is important for the maintenance of joint function. In various osteoarthritis (OA) diseases, chondrocytes undergo a series of pathophysiological changes, leading to the loss of chondrocytes and the degradation of extracellular matrix (ECM). Here, cytoplasmic localized histone deacetylase 6 (HDAC6) is found to be up-regulated on the articular surface in DMM-induced mouse OA model. Since HDAC6 is highly related to the acetylation of tubulin, and the function of the microtubule system is closely related to material transport, signal transduction, etc. The relationship between the expression level or activity of HDAC6 and the fate of chondrocytes in vitro and in vivo were confirmed. Primary chondrocytes overexpressing DNA-HDAC6 with plasmid were constructed in vitro, and HDAC6 inhibitor Tubastatin A was selected to inhibit HDAC6 enzyme activity in vivo and in vitro. Subsequently, mitochondrial spatial arrangement, degradation of ECM and pathological changes in joint were defined. The results show that overexpression of HDAC6 causes mitochondrial dysfunction and promotes ROS production, leading to degradation of ECM. Whereas Tub...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research