Alkaline phosphatase expression during monocyte differentiation - Overlapping markers as a link between monocytic cells, dendritic cells, osteoclastsand osteoblasts

Human monocytes (Mo) in culture can be differentiated into macrophages (M p hi), dendritic cells (DC) and osteoclasts. In addition, we have established a Mo-derived in vitro granuloma model which here was compared with ex-vivo isolated foreign body granuloma cells. In these models overlapping phenoty pes developed between monocyte-derived dendritic cells (MoDC), osteoclasts, M phi, and osteoblasts. In Mo cultures granulomas were induced by immobili zed particulate material. AP activity (osteoblast marker) was found to be c o-expressed with cytoplasmic tartrate resistant acid phosphatase (TRAP) as a marker of osteoclasts. While proliferating, the number of AP(+) cells dec reased, being replaced by cells co-expressing the osteoclast markers vitron ectin receptor (VNR) and TRAP. Coexpression of the Mo/M phi marker CD68 wit h AP or VNR confirmed the monocytic origin of the cells. When Mo were treat ed with interleukin-4 (IL-4), the number of AP(+) cells markedly increased and remained stably expressed over 12 days. In explants from ex vivo granul omas obtained from endoprosthetic revisions the major cell type was the AP( +) cell co-expressing CD68. The bone-specific alkaline phosphatase (BAP) as a marker of osteoblasts was detected by FAGS analysis in the ex vivo granu loma cells. By RT-PCR the mRNA for osteocalcin, which is a highly specific marker fur osteoblasts, was detected. From our results we conclude an ontog enetic relationship between macrophages, DC and osteoclasts. Furthermore, t he data suggest a transdifferentiation between Mo and osteoblasts.