Mutations in the human cathepsin K (CTSK) cause pycnodysostosis, an autosomal recessive disease characterized by short stature and elevated bone density (osteopetrosis). In mice, global deletion of Ctsk results in decreased bone resorption and osteopetrosis, but also enhances the rate of bone formation. To determine the role of CTSK in bone formation, Sutada Lotinun and colleagues generated osteoclast- and osteoblast-specific Ctsk knockout mice. The accompanying confocal microscopy images show osteoclasts stained with antibodies against the secretory lyosomal marker synaptotagmin 7 (green), actin (phalloidin/red), and nuclei (stained with To-Pro/blue). Lotinun and colleagues identified molecular mechanisms explaining how loss of CTSK enhances bone formation. CTSK inhibitors are currently being assessed in human clinical trials for the treatment of osteoporosis.
Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of
Sutada Lotinun, Riku Kiviranta, Takuma Matsubara, Jorge A. Alzate, Lynn Neff, Anja Lüth, Ilpo Koskivirta, Burkhard Kleuser, Jean Vacher, Eero Vuorio, William C. Horne, Roland Baron