Colony-stimulating factor-1 (CSF-1) rescues osteoblast attachment, survival and sorting of beta-actin mRNA in the toothless (tl-osteopetrotic) mutation in the rat

We have shown that in the osteopetrotic rat mutation toothless (tl) osteobl asts are absent from older bone surfaces in mutants and that mutant osteobl asts in vivo lack the prominent stress fiber bundles polarized along bone s urfaces in osteoblasts from normal littermates. Our recent data demonstrate that in normal osteoblasts in vitro beta- and gamma-actin mRNAs have diffe rent, characteristic intracellular distributions and that tl (mutant) osteo blasts fail to differentially sort these mRNAs. Because bone resorption and formation are highly interdependent and injections of CSF-1, a growth fact or, increase bone resorption and growth in tl rats, we examined the effects of CSF-1 treatment on osteoblast survival and ultrastructure in vivo and a bility to sort actin mRNAs in vitro. Neonatal CSF-1 treatment of mutants re stores osteoblasts on older bone surfaces, normalizes the intracellular dis tribution of stress fibers in osteoblasts in vivo and promotes normal sorti ng of beta-actin mRNA in mutant osteoblasts in vitro without normalizing ga mma-actin distribution. These data suggest the beta- and gamma-actin mRNAs in osteoblasts are sorted by different mechanisms and that the differential sorting of beta-actin mRNA is related to the characteristic polarization o f stress fibers in osteoblasts and their survival on bone surfaces. This ex perimental system can be used to explore the relationships and regulation o f these aspects of cell and tissue biology.