Myeloid blasts are the mouse bone marrow cells prone to differentiate into osteoclasts

Abstract

Cells of the myeloid lineage at various stages of maturity can differentiate into multinucleated osteoclasts. Yet, it is unclear which developmental stages of this lineage are more prone to become osteoclasts than others. We investigated the osteoclastogenic potential of three successive stages of myeloid development isolated from mouse bone marrow. Early blasts (CD31hi/Ly-6C-), myeloid blasts (CD31+/Ly-6C+), and monocytes (CD31-/Ly-6Chi), as well as unfractionated marrow cells, were cultured in the presence of M-CSF and receptor activator of NF-B ligand (RANKL), and the differentiation toward multinucleated cells and their capacity to resorb bone was assessed. Myeloid blasts developed rapidly into multinucleated cells; in only 4 days, maximal numbers were reached, whereas the other fractions required 8 days to reach maximal numbers. Bone resorption was observed after 6 (myeloid blasts and monocyte-derived osteoclasts) and 8 (early blast-derived osteoclasts) days. This difference in kinetics in osteoclast-forming capacity was confirmed by the analysis of osteoclast-related genes. In addition, the myeloid blast fraction proved to be most sensitive to M-CSF and RANKL, as assessed with a colony-forming assay. Our results show that osteoclasts can develop from all stages of myeloid differentiation, but myeloid blasts are equipped to do so within a short period of time.

Immune complex-induced inhibition of osteoclastogenesis is mediated via activating but not inhibitory Fcγ receptors on myeloid precursor cells

“…Osteoclast progenitors within the bone marrow are present at various stages of maturity and, as a result, differ in their potential to differentiate into osteoclasts 30. Based on the expression of CD31 and Ly-6C, the composition of bone marrow subpopulations of WT and FcγRIIB −/− mice was shown to be comparable (figure 4A).…”

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

“…Next, we determined the composition of osteoclast precursors in the bone marrow, using flow cytometry. Using monoclonal antibodies recognizing CD31 (ER-MP12) and Ly-6C (ER-MP20) (21), 6 subpopulations were discriminated, of which early blast cells (CD31 high /Ly-6CϪ), myeloblasts (CD31ϩ/Ly-6Cϩ), and monocytes (CD31Ϫ/Ly-6C high ) are the populations that give rise to osteoclasts (23). Compared with WT mice, S100A9-deficient mice displayed increased percentages of myeloblasts, monocytes, and granulocytes (mean Ϯ SEM 6.5 Ϯ 0.3% versus 8.1 Ϯ 0.2%, 6.7 Ϯ 0.3% versus 8.3 Ϯ 0.4%, and 23.5 Ϯ 0.9% versus 27.4 Ϯ 0.7%, respectively, for WT versus S100A9-deficient bone marrow cells), whereas no differences were detected in the composition of the remaining subpopulations (Figure 2A).…”

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

“…Therefore, bone marrow, which is relatively rich in hematopoietic stem cells including osteoclast precursors, may be the source from which precursors differentiate into osteoclasts in physiological bone turnover [6]. However, in some cases of pathological bone resorption, such as in rheumatoid arthritis where bone of the joints is eroded, osteoclasts are formed in an area where no bone marrow is available.…”