Effects of macrophage colony stimulating factor and granulocyte‐macrophage colony stimulating factor on osteoclastic differentiation of hematopoietic progenitor cells

Abstract

Although the hematopoietic origin of the osteoclast is generally accepted, the precise phenotype of the progenitor and the regulation of its differentiation are unclear. This study compares proliferation and differentiation of progenitors in response to macrophage colony stimulating factor (M-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF). Nonadherent progenitor cells from murine long-term bone marrow cultures (LTBMC) (as a source of osteoclast progenitors) demonstrated a significant proliferative response to M-CSF. In addition, M-CSF increased the number of multinucleated cells, only a small percent of which (14-16%) were tartrate-resistant, acid phosphatase (TRAP)-positive. In contrast, cells cultured with GM-CSF generated more TRAP-positive multinucleated cells even at concentrations less stimulatory of proliferation than M-CSF. The osteoclast phenotype of these multinucleated cells was also assessed by ultrastructural characterization of ruffled borders in association with bone fragments. The bone-active hormone 1,25-dihydroxyvitamin D3 inhibited the proliferation of this subset of progenitor cells in the presence of M-CSF or GM-CSF. All of these results show effects on progenitors in the absence of the stromal cell microenvironment in this system. These results provide evidence for a divergence in the biological responsiveness of osteoclast progenitor cells to M-CSF compared with GM-CSF; they support the notion that M-CSF has a "priming" effect on osteoclast progenitors whose subsequent differentiation to osteoclastic multinucleated cells is promoted by GM-CSF.

Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy.

“…However, more recent findings suggest that many of these cytokines may also affect other cell lineages. For example, G-CSF has been shown to act in synergy with IL-3 or KL to trigger very early hematopoietic progenitors into the cell cycle, and M-CSF affects placental development and osteoid cells (43)(44)(45). Of considerable interest for the present studies, Epo has been shown to augment megakaryocyte formation in the presence of aplastic serum, a known source of TPO (23,24), and to expand not only erythroid but also megakaryocyte and granulocytic progenitors in Epo-treated patients (46).…”

Prostaglandin G/H synthase-2 is required for maximal formation of osteoclast-like cells in culture

“…However, there are conflicting reports on the effects of GM-CSF on osteoclastogenesis in marrow cultures and cocultures. GM-CSF has been found to increase OCL formation in human and primate bone marrow cultures (56,57) and in some rodent cultures (58)(59)(60). On the other hand, there are many studies in murine marrow cultures and coculture systems showing that GM-CSF inhibits OCL formation (45,46,(61)(62)(63), and it has been proposed that GM-CSF inhibits OCL formation by inhibiting expression of integrin αvβ5 (64).…”

Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid arthritis: comparison with IL1 and tumour necrosis factor

“…Here we used the purified T cells and the cell density or concentration of IL18 was not as high as in their study. Several reports also state that GM-CSF can stimulate osteoclast formation in vitro [35][36][37] and in vivo. 38 These data do not support the statement that GM-CSF mediates the inhibitory effect of IL18 on osteoclastogenesis.…”