Lack of requirement of osteopontin for inflammation, bone erosion, and cartilage damage in the K/BxN model of autoantibody-mediated arthritis.
OBJECTIVE
Osteopontin (OPN) is a secreted glycoprotein involved in a range of physiologic processes, including inflammation, immunity mediated by Th1 cells, and bone remodeling. It is expressed in the joints of rheumatoid arthritis patients and has been the subject of conflicting reports concerning its role in arthritis induced by antibodies against type II collagen. This study assessed the role of OPN in the K/BxN serum-transfer model of autoantibody-induced arthritis.


METHODS
Expression of OPN gene transcripts was assessed by microarray analysis of ankle RNA taken at 6 time points after transfer of K/BxN serum. OPN-sufficient or OPN-deficient littermates backcrossed for 10 generations onto the C57BL/6 genetic background were given K/BxN serum. Arthritis severity was measured by ankle thickening and a clinical index. Hind limb sections were stained with hematoxylin and eosin or toluidine blue and scored for inflammation, cartilage damage, and bone erosion.


RESULTS
OPN messenger RNA transcripts progressively increased in ankle joints during the course of K/BxN serum-transferred arthritis. OPN-deficient mice receiving K/BxN serum developed arthritis with kinetics and clinical severity comparable with those of OPN-sufficient littermates. Histologic assessment of arthritic joints from OPN-deficient mice revealed synovial hyperplasia, pannus formation, mononuclear cell infiltration, bone erosion, cartilage damage at sites adjacent to and distal from pannus invasion, and tartrate-resistant acid phosphatase-positive multinucleated cells at sites of bone erosion. Histopathologic scoring demonstrated comparable levels of inflammation, cartilage damage, and bone erosion in OPN-sufficient and OPN-deficient mice.


CONCLUSIONS
OPN does not have a required role in inflammation, bone erosion, and cartilage damage in the K/BxN serum-transfer model.
Jacobs
Jonathan P
JP
Joslin Diabetes Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02215, USA.
Pettit
Allison R
AR
Shinohara
Mari L
ML
Jansson
Marianne
M
Cantor
Harvey
H
Gravallese
Ellen M
EM
Mathis
Diane
D
Benoist
Christophe
C
D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000503:physiopathology*; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D001842:Bone and Bones / Q000473:pathology*; D002356:Cartilage / Q000473:pathology*; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D001323:Autoantibodies; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin