Section B Project B04

Histocytometric and molecular assessment of the inflammatory osteoclastogenic niche in situ

Within living tissues, osteoclasts do not function in isolation, but instead require the concerted delivery of distinct molecular signals by a cellular microenvironment that represents a still undefined pro-osteoclastogenic niche. The aim of this project is a comprehensive characterization of this osteoclastsupporting milieu, its composition, and molecular determinants in unprecedented spatial and temporal resolution in vivo. Specifically, the project investigates the hypothesis that osteoclast development is in fact preceded by the formation of a specific stromal niche that actively attracts precursors and facilitates their differentiation. By applying a tissue-level volume bioimaging approach together with innovative imaging analysis and visualization techniques as well as niche-specific transcriptional profiling, B04 will quantitatively assess bone degradation in experimental arthritis or periodontitis in situ in correlation with its adjacent cellular microenvironment. The long-term perspective of the project is to gain a detailed understanding of the tissue-level determinants that ultimately lead to inflammatory bone loss in vivo.