Arthritis and the role of endogenous glucocorticoids

Abstract

Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

“…Nuclear receptor subfamily 3 group C member 1 ( NR3C1 ) encodes the glucocorticoid receptor (GR) which circulates in the cytoplasm and is involved in the inflammatory response ( Escoter-Torres et al., 2019 ). In osteoarthritis, endogenous glucocorticoid signaling in osteoblasts and chondrocytes is detrimental ( Macfarlane et al., 2020 ).…”

The Role of Glucocorticoids in Inflammatory Diseases

“…Interestingly, endogenous GCs seem to have dual effects in RA. Anti-inflammatory activities are established in macrophages, mast cells, and chondrocytes, whereas GCs exert pro-inflammatory effects in osteoblasts, myocytes, and FLS [ 149 ]. Mice overexpressing the GC-inactivating enzyme 11β-HSD2 in osteoblasts showed an attenuated local inflammatory activity and clinical signs of arthritis [ 150 ], whereas mice carrying a specific deletion of the GR in chondrocytes developed exaggerated clinical symptoms in the STIA and AIA models.…”

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model

“…38,39 Rheumatoid Arthritis is a chronic inflammatory disease characterized by joint inflammation that induces cartilage destruction. 40,41 As Coll type II degradation may indicate cartilage destruction in the joints of RA patients, it is an important parameter to evaluate since it can be useful as a disease-specific biomarker. 42,43 In this sense, the immunofluorescence staining was performed to qualitatively evaluate the presence of Coll type II in the chondrogenic cells matrix, under the three conditions: healthy THP-1 cells cultured with hCH, inflamed THP-1 cultured with hCH, and inflamed THP-1 cultured with hCH, and with NPs-Hydrogel treatment after 7 days of culture (Fig.…”