Macrophage colony stimulation factor expression in bone marrow is reduced following erythropoietin treatment in mice: a combinatorial analysis of expression levels and cell populations

Bone metabolism is influenced by a myriad of therapeutic interventions. Erythropoietin (EPO) serves as a key regulator of erythropoiesis and is used in clinical practice for the treatment of anemia. We and others have shown that EPO induces bone resorption and trabecular bone loss in mice. Osteoclasts, the bone-resorbing cells, originate from myeloid precursors while macrophage colony-stimulating factor (MCSF) is essential for their development and survival.

We explored the dynamics of MCSF expression in bone marrow (BM) following EPO administration. C57BL6/J mice were injected with EPO or diluent. BM samples were subjected to qRT-PCR for gene expression. Unexpectedly, we found a twofold reduction in the expression of MCSF in the EPO-injected mice. As the BM contains a wide range of MCSF-expressing cells, we determined MCSF expression levels in sorted erythroblasts, granulocytes, monocytes, B and T cells, basophils, and mesenchymal cells. There was a twofold increase in erythroblasts and a 2-3-fold decrease in all other populations except monocytes and basophils. MCSF expression was most pronounced in granulocytes accounting for 71-74% of total MCSF expression in the sorted cells. As EPO did not affect granulocyte MCSF expression, the reduction in total MCSF expression can be explained by the two-fold decrease in granulocyte population (24±5% to 12±3%).

We propose that EPO-mediated reduction in BM MSCF is mostly due to the shrinkage of the granulocyte population. Further research is warranted to resolve the role of granulocytes in bone metabolism and the biological rationale for the downregulation of MCSF in conditions associated with bone loss.