Inhibition of CatK activity
in human osteoclasts (OCs). (A) Maturation
of OCs from monocytes. (B) CD14+ monocytes on bone slices were treated
with M-CSF (day 0) and RANKL (day 3) to stimulate differentiation
to mature OCs. Medium containing either inhibitor or DMSO was refreshed
on day 7, 10, 13, and 16. At day 21, OCs were washed away and lysed,
and bone slices were stained to visualize bone resorption. (C) Bone
resorption visualized by staining of resorption pits with Coomassie
Brilliant Blue. More staining means more resorption pits and, thus,
more bone resorption activity. Normal OCs predominantly form deep
trenches (paths), while OCs lacking CatK form small pits (circular
dots). (D) Schematic overview of CatK activation. (E) CatK activity
and expression in OC lysates. Top: fluorescence scan of CatK bound
to irreversible activity-based probe BMV109 shows mature, active CatK.
Middle/bottom: Western blotting against CatK shows total amount of
CatK present in OC lysates. Darker bands indicate more CatK activity/expression.