Transgenic Disruption of Glucocorticoid Signaling in Osteoblasts Attenuates Joint Inflammation in Collagen Antibody-Induced Arthritis.

Transgenic Disruption of Glucocorticoid Signaling in Osteoblasts Attenuates Joint Inflammation in Collagen Antibody-Induced Arthritis. Am J Pathol. 2016 Mar 14; Authors: Tu J, Zhang Y, Kim S, Wiebe E, Spies CM, Buttgereit F, Cooper MS, Seibel MJ, Zhou H Abstract The role of endogenous glucocorticoids (GCs) in rheumatoid arthritis remains unclear. Herein, we examined the role of osteoblastic GC signaling in collagen antibody-induced arthritis. Intracellular GC signaling was abrogated exclusively in mature osteoblasts via transgenic (tg) expression of 11ß-hydroxysteroid dehydrogenase type 2. Arthritis was induced in 8-week-old male tg mice and their wild-type (WT) littermates. Paw swelling was scored daily from induction to end point (day 14). Inflammation, cartilage degradation, and local bone erosion were assessed at the wrist, knee, and ankle joints. Systemic skeletal changes were determined by microcomputed tomography and histomorphometrical analysis of the tibiae. Both tg and WT mice developed acute arthritis in response to the administration of collagen antibodies. However, compared with WT mice, both clinical and histological indexes of joint inflammation were significantly mitigated in animals with disrupted osteoblastic GC signaling. In WT mice, arthritis was associated with increased bone resorption, decreased bone formation, and significant bone loss. In contrast, bone turnover and bone mass remained unchanged in tg arthrit...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research