title: Alkaline phosphatase expression during monocyte differentiation. Overlapping markers as a link between monocytic cells, dendritic cells, osteoclasts and osteoblasts.
abstract: Human monocytes (Mo) in culture can be differentiated into macrophages (M phi), 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 phenotypes developed between monocyte-derived dendritic cells (MoDC), osteoclasts, M phi, and osteoblasts. In Mo cultures granulomas were induced by immobilized particulate material. AP activity (osteoblast marker) was found to be co-expressed with cytoplasmic tartrate resistant acid phosphatase (TRAP) as a marker of osteoclasts. While proliferating, the number of AP+ cells decreased, being replaced by cells co-expressing the osteoclast markers vitronectin receptor (VNR) and TRAP. Coexpression of the Mo/M phi marker CD68 with AP or VNR confirmed the monocytic origin of the cells. When Mo were treated with interleukin-4 (IL-4), the number of AP+ cells markedly increased and remained stably expressed over 12 days. In explants from ex vivo granulomas 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 FACS analysis in the ex vivo granuloma cells. By RT-PCR the mRNA for osteocalcin, which is a highly specific marker for osteoblasts, was detected. From our results we conclude an ontogenetic relationship between macrophages, DC and osteoclasts. Furthermore, the data suggest a transdifferentiation between Mo and osteoblasts.
authors.affiliation: Department of Maxillofacial Surgery, Georg-August-University Goettingen, Germany.
authors.forename: D E
authors.initials: DE
authors.lastname: Heinemann
authors.forename: H
authors.initials: H
authors.lastname: Siggelkow
authors.forename: L M
authors.initials: LM
authors.lastname: Ponce
authors.forename: V
authors.initials: V
authors.lastname: Viereck
authors.forename: K G
authors.initials: KG
authors.lastname: Wiese
authors.forename: J H
authors.initials: JH
authors.lastname: Peters
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D015415:Biomarkers; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000201:enzymology*; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology; D010010:Osteoclasts / Q000166:cytology / Q000201:enzymology
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase