engleski

OSTEOPROTEGERIN AS A MEDIATOR OF BONE PHENOTYPE IN MURINE GENERALISED LYMPHOPROLIFERATIVE DISORDER

We have previously shown that mice with generalised lymphoproliferative disorder (gld) have increased bone mass in addition to autoimmune disease characterised by the accumulation of double negative (dn) T lymphocytes (CD3+CD4&#8211; CD8&#8211; B220+). To further explore the association of the immune disorder with the bone phenotype of gld mice, we established parabiotic circulation between gld and wild-type animals (C57BL/6, B6). The mice were sacrificed weekly for four weeks or, in the second set of experiments, were separated after four weeks of parabiosis and sacrificed two weeks following the separation. One week after the surgery, the proportion of dn T lymphocytes increased in peripheral blood and lymphatic tissues of wild-type members of the B6-gld parabiotic pair and decreased in tissues of gld pair members. The mixing of cells continued during four weeks of parabiosis. Moreover, the proportions of dn T cells in tissues of gld members of the B6-gld pairs after the separation became indistinguishable to those in control B6 animals. Number of osteoclast-like (OCL) cells in bone marrow cultures from a wild-type member of B6-gld parabiotic pair at the end of the first week decreased from 266&plusmn ; ; 52 to 120&plusmn ; ; 5 OCL/cm2, P<0.05, comparable with gld mice (99&plusmn ; ; 21 OCL/cm2), while the number of osteoblast colonies did not change. After four weeks, number of OCL cells formed from the bone marrow of B6 parabiotic mice was still similar to the number of OCL cells in their gld counterparts (150&plusmn ; ; 18 and 131&plusmn ; ; 24 OCL/cm2, respectively). In addition, the number of osteoblast colonies in B6 members of B6-gld parabiotic pairs increased (from 6&plusmn ; ; 2 to 18&plusmn ; ; 1 colonies/cm2, P<0.05) thus resembling the cell cultures of gld mice (18&plusmn ; ; 1 colonies/cm2). The alterations of osteoclastogenic and osteoblastogenic potential of the bone marrow of B6 members of B6-gld parabiotic pairs were paralleled by changes in the osteoprotegerin (OPG) expression. Levels of OPG in the bones of B6 mice, as assessed both by quantitative PCR and ELISA, increased during parabiosis and reached the levels found in gld animals. Taken together, these data show that the circulation of cells, including dn T lymphocytes, established by parabiosis confers the osteoclast and osteoblast phenotype of gld to wild-type animals. Those changes are likely to be mediated through OPG, although the exact mechanism remains to be determined.

bone; Fas ligand; parabiosis

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