Structural, cellular, and molecular evaluation of bone erosion in experimental models of rheumatoid arthritis: assessment by μCT, histology, and serum biomarkers.
Bone erosion is a clinical endpoint for various diseases including rheumatoid arthritis. In this paper, we used rodent arthritis models with severe bone erosion to examine the structural, cellular, and molecular aspects of the inflammation-driven bone resorption process. Our data show that bone loss is observed only in chronically, severely inflamed joints. The most severely affected anatomic sites were the metatarsal phalangeal joint and tarsal bones of the paw. The magnitude of the inflammation-driven bone erosion was dependent on both the duration of inflammatory response and the severity of the joint swelling response. The application of micro-computed tomography well demonstrated the therapeutic benefit of anti-IL-17A in protection of bones from erosion. Alterations in the cellular profile of the joint occurred prior to any major structural deterioration of the bone. Receptor activator for nuclear factor κB ligand, a potent inducer of osteoclast differentiation and bone resorption, was elevated in animals coincident with severe arthritis initiation. The experimental approaches and concepts outlined in this paper provide a valuable process to evaluate and quantify therapies that modulate rodent arthritis-associated bone-erosion models.
Chao
Cheng-Chi
CC
Department of Immunology, Schering Plough Biopharma (formerly DNAX Research Institute), 901 California Avenue, Palo Alto, CA 94304, USA.
Chen
Shi-Juan
SJ
Adamopoulos
Iannis E
IE
Judo
Michael
M
Asio
Agelio
A
Ayanoglu
Gulesi
G
Bowman
Edward P
EP
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001862:Bone Resorption / Q000276:immunology* / Q000503:physiopathology; D005528:Foot / Q000503:physiopathology; D006651:Histocytochemistry; D020381:Interleukin-17 / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D053245:RANK Ligand / Q000097:blood; D051381:Rats; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; D020381:Interleukin-17; D053245:RANK Ligand