Histone deacetylase-4 and histone deacetylase-8 regulate interleukin-1β-induced cartilage catabolic degradation through MAPK/JNK and ERK pathways

Abstract

Interleukin-1β (IL-1β)-induced inflammatory response is associated with osteoarthritis (OA) and its development. Histone deacetylase (HDAC) may be involved in regulating this pathogenesis, but the mechanism has yet to be elucidated. The aim of the present study was to investigate the mechanism underlying the regulation of IL-1β-stimulated catabolic degradation of cartilage by HDAC. An in vitro model of OA was generated using rat articular chondrocytes (rACs) treated with IL-1β. The role of HDAC in IL-1β-induced gene expression was investigated using HDAC inhibitors and specific small interfering RNAs (siRNAs). The association of diverse mitogen-activated protein kinase (MAPK) pathways was examined. The IL-1β-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5, and the production of collagen X and cyclo-oxygenase-2 in rACs was accompanied by the expression of HDAC4 and HDAC8, and were significantly downregulated by HDAC inhibitors and specific siRNAs. IL-1β-induced activation of extracellular signal-regulated kinase was downregulated by the HDAC inhibitor Trichostatin A, but not significantly by PCI-34051. The activation of c-Jun N-terminal kinase was observably downregulated by the latter, but only slightly by the former. These results suggest that HDAC4 and HDAC8 may serve as key upstream mediators of MAPK in regulating the IL-1β-induced cartilage catabolic and degradation. Therefore, inhibiting HDAC4 or HDAC8 or both may be a promising therapeutic strategy in preventing and treating OA.

Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

“…The MAPK signaling pathway, which is a group of serine/threonine protein kinases involved in the cellular signal transduction [60], which regulated many cellular functions, affects a large number of human diseases. Previous studies have demonstrated the effect of MAPK signals on tumor metastasis [61,62], osteogenesis [63,64], osteoarthritis [65,66], or certain inflammatory diseases [67]. For example, it can regulate the proliferation and differentiation of brain cells [68].…”

Icariin Activates Autophagy via Down-Regulation of the NF-κB Signaling-Mediated Apoptosis in Chondrocytes

“…In addition, it also had a better reversal effect than PDTC, i.e., on the negative effect of TNF-α-induced autophagy inhibition and apoptosis activation. Previous studies reported that in addition to the NF-κB signaling pathway, other signaling pathways such as the MAPK/JNK and ERK pathways are also involved in the pathogenesis process of OA ( Wang et al, 2018 ). In the future experiments, we would like to verify whether icariin protects against OA via these or other signaling pathways.…”

Effects of IL-1β-induced ADAMTS-4/-5 and TAK1 on the degradation of cartilage aggrecan in the progression of human osteoarthritis

“…With the rapid aging of global population, the incidence rate of OA has increased in recent years, and the morbidity is > 10%. [4,18]. OA is a chronic progressive joint disease, characterized by arthrosynovitis, degeneration and destruction of cartilage, subchondral bone sclerosis, and osteophyte formation [19].…”

“…OA is a common orthopedic disease among the elderly and a chronic, in ammation-related progressive degenerative disease characterized by destruction of cartilage and aggrecan degradation of cartilage extracellular matrix (ECM), which is affected by many risk factors, such as gender, age, obesity, in ammation, and trauma [2,3]. Although the pathogenesis of OA remains to be elucidated, it is speculated that the imbalance between anabolism and catabolism in cartilage ECM contributes to the progression of OA [1,4]. Previous researchers have shown that collagens and aggrecan are the key components of cartilage ECM [5].…”