Immortalized fibroblastoid cells of osteopetrotic mutant mice (op/op) do not secrete CSF-1 and do not inhibit CSF-1 activity released by normal cells

Abstract

Osteopetrotic mutant mice (op/op) are deficient in osteoclasts and macrophages. In this report, the establishment of clonal permanent fibroblastoid cell lines from spleens of op/+ and op/op mice is described and conditioned medium obtained from these cell lines examined for release of growth factor that stimulates the proliferation and differentiation of macrophage precursor cells. It is shown that conditioned medium of op/+ fibroblastoid cells contains CSF-1 activity, whereas conditioned medium of op/op fibroblastoid cells does not. Conditioned medium of op/op cell lines does not inhibit colony-stimulating factor 1 (CSF-1) activity in conditioned medium of op/+ cells. Hybrids between op/op and op/+ fibroblastoid cells release CSF-1 activity in amounts similar to op/+ cell lines alone. These results confirm that op/op mice do not produce any CSF-1 activity. The data further suggest that predicted truncated proteins expressed from the mutated CSF-1 gene in op/op mice are functionally not relevant and that there is no evidence for trans-acting factors in op/op that might inhibit CSF-1 expression.