title: Transgenic Disruption of Glucocorticoid Signaling in Osteoblasts Attenuates Joint Inflammation in Collagen Antibody-Induced Arthritis.
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 arthritic mice. Disruption of GC signaling in osteoblasts significantly reduces joint inflammation and prevents structural bone and cartilage damage in collagen antibody-induced arthritis. These data corroborate the concept that osteoblasts modulate the inflammatory response in immune-mediated arthritis via a GC-dependent pathway.
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Tu
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kim
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Wiebe
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Spies
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.affiliation: Department of Endocrinology and Metabolism, Concord Repatriation Hospital, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cooper
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia; Department of Endocrinology and Metabolism, Concord Repatriation Hospital, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Seibel
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia. Electronic address: h.zhou@sydney.edu.au.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology*; D005938:Glucocorticoids / Q000502:physiology*; D008297:Male; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology*; D010011:Osteocytes / Q000473:pathology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013264:Stifle / Q000473:pathology / Q000502:physiology; D013585:Synovitis / Q000473:pathology / Q000503:physiopathology; D055114:X-Ray Microtomography
chemical_list: D005938:Glucocorticoids