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Osteopontin as a positive regulator in the osteoclastogenesis of arthritis
Ist Teil von
Biochemical and biophysical research communications, 2004-04, Vol.316 (3), p.809-815
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2004
Quelle
MEDLINE
Beschreibungen/Notizen
We examined the role of osteopontin (OPN) in the osteoclastogenesis of arthritis using collagen-induced arthritis (CIA). Cells from arthritic joints of wild-type (OPN +/+) mice spontaneously developed bone-resorbing osteoclast-like cells (OCLs). The cultured cells showed an enhanced expression of receptor activator of nuclear factor κB ligand (RANKL) and a decreased expression of osteoprotegerin (OPG). The addition of OPG reduced the number of OCLs, indicating that the osteoclastogenesis depends on the RANK/RANKL/OPG system. The cells also produced OPN abundantly and anti-OPN neutralizing antibodies suppressed the development of OCLs. Moreover, the addition of OPN increased the expression of RANKL and augmented differentiation of OCLs from OPN-deficient (OPN −/−) cells. OPN, like the combination of 1α,25-dihydroxyvitamin D
3 and dexamethasone, also enhanced the RANKL expression and decreased OPG expression in a stromal cell line, ST2. These results suggest that OPN acts as a positive regulator in the osteoclastogenesis of arthritis through the RANK/RANKL/OPG system.