Monocytes Do Not Transdifferentiate into Proper Osteoblasts

Abstract

Recent publications suggested that monocytes might be an attractive cell type to transdifferentiate into various cellular phenotypes. Aim was, therefore, to evaluate the potential of blood monocytes to transdifferentiate into osteoblasts. Monocytes isolated from peripheral blood were subjected to two previously published treatments to obtain unique, multipotent cell fractions, named programmable cells of monocytic origin (PCMOs) and monocyte-derived mesenchymal progenitor cells (MOMPs). Subsequently, MOMPs and PCMOs were treated with osteogenic differentiation medium (including either vitamin D or dexamethasone) for 14 days. Regarding a variety of surface markers, no differences between MOMPs, PCMOs, and primary monocytes could be detected. The treatment with osteogenic medium neither resulted in loss of hematopoietic markers nor in adoption of mesenchymal phenotype in all cell types. No significant effect was observed regarding the expression of osteogenic transcription factors, bone-related genes, or production of mineralized matrix. Osteogenic medium resulted in activation of monocytes and appearance of osteoclasts. In conclusion, none of the investigated monocyte cell types showed any transdifferentiation characteristics under the tested circumstances. Based on our data, we rather see an activation and maturation of monocytes towards macrophages and osteoclasts.

Co-cultures of programmable cells of monocytic origin and mesenchymal stem cells do increase osteogenic differentiation

“…and ). Schmitt et al reported similar results in 2012 and in contrast their experiments indicated that PCMOs may differentiate into osteoclasts if cultured in the presence of osteogenic stimuli . One reason for this could be the low CD90 expression as found by our FACS analysis.…”

“…On the other hand M‐CSF and RANKL were used for the in vitro generation of osteoclasts . So it is not surprising that PCMOs tend to differentiate into osteoclasts and osteoclasts were shown to accelerate the osteogenic differentiation of MSCs in vitro . Preliminary results of our group indicate an increase of osteoclastic marker genes (MMP‐9, CALCR2, TRACP5) during PCMO dedifferentiation phase.…”

“…It is still under debate if cells of the mononuclear lineage can be differentiated into cells of mesenchymal lineage . While Schmitt et al were not able to redifferentiate PCMOs into osteoblasts in 2012, recent studies indicate that mononuclear cells at least support the differentiation of MSCs into osteoblast‐like cells .…”

Primary human osteoblasts with reduced alkaline phosphatase and matrix mineralization baseline capacity are responsive to extremely low frequency pulsed electromagnetic field exposure — Clinical implication possible

“…Following overnight adherence, medium was changed to dedifferentiation medium (Alpha MEM, 10% FCS, 2 mM l -glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin, 2.5 ng/ml rhM-CSF) for 6 days. Osteoclast differentiation was induced by differentiation medium (Alpha MEM, 10% FCS, 2 mM l -glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin, 20 ng/ml rhRANKL) for 21 days (Schmitt et al, 2012). …”

“…Signals were normalized to relative cell numbers by Resazurin conversion. Trap5B staining was performed as described (Schmitt et al, 2012). …”