Lack of requirement of osteopontin for inflammation, bone erosion, and cartilage damage in the K/BxN model of autoantibody-mediated arthritis

Joslin Diabetes Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02215, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 08/2004; 50(8):2685-94. DOI: 10.1002/art.20381
Source: PubMed


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.
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.
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.
OPN does not have a required role in inflammation, bone erosion, and cartilage damage in the K/BxN serum-transfer model.

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    • "Other pro-inflammatory factors in antibody-mediated arthritis – which may be generated by osteoblasts in a GC-dependent way – are urokinase-type plasminogen activator (u-PA) [41-43], matrix metalloproteinases (MMP) [18,43] and macrophage migration inhibitory factor (MIF) [44-46]. Osteopontin and IL-6 are rather unlikely to be responsible because they play no essential role in K/BxN arthritis [16,37]. "
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    • "It was found that its level is increased in RA., Its exact role in RA is however still unclear. It was noticed by one group that OPN knocked out mice were protected against RA [114], yet another group of researchers failed to produce the same conclusions [115]. Overexpression of OPN is also noticed in a variety of cancers, including lung, breast, colorectal and stomach cancer. "
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    • "Mitigation of experimental autoimmune encephalomyelitis and collagen-induced arthritis have been reported in the absence of osteopontin, although the latter finding is controversial and has not been observed by others (38–41). Moreover, the serum transfer model of arthritis is not altered by the absence of osteopontin (39). From these data, it is evident, however, that the interaction of osteopontin with CD44 is not a relevant factor for arthritic bone erosion. "
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