BoneKEy Reports | BoneKEy Watch

In situ and in vivo visualization of mature osteoclasts reveals new insights

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DOI:10.1038/bonekey.2013.79

Kikuta et al. used a novel technique to visualize mature osteoclasts in situ in mouse bone to observe their activity and their responses to key stimuli. Intravital multiphoton microscopy of the exposed calvarial bones of fluorescent reporter mice, which express green fluorescent protein (GFP) in their osteoclasts, allowed the researchers to observe the behavior of mature osteoclasts at the ruffled border of bone surfaces.

The osteoclasts cycled between a static state, in which they were resorbing bone, to an active, motile state in which they showed no resorbing activity. The addition of RANKL, a factor that activates osteoclasts, converted motile nonresorbing osteoclasts into static bone-resorbing cells. The researchers also noted that adding Th17 cells, CD4+ T cells that express RANKL, rapidly converted motile, nonresorbing cells into stationary osteoblasts that actively resorbed bone. This conversion was mediated by cell-to-cell contact between the Th17 cells and osteoblasts.

Editor’s comment: This is an elegant intravital visualization of GFP-labeled osteoclasts using multiphoton microscopy. The finding that mature osteoclasts cycle between static bone-resorptive and motile but inactive states was entirely unanticipated, as was the cell–cell contact-mediated activation of osteoclasts by RANKL-expressing Th17 cells. Both events have the potential to become novel therapeutic targets.

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