MOLECULES

Full name: Cathepsin K

Aliases: CTSO, PKND, PYCD, CTS02, CTSO1, and CTSO2¹

Size: Immunoglobulin superfamily²

Family: Papain-like cysteine protease member of the cathepsin family of lysosomal proteases (cathepsins B, C, F, H, K, L, O, S, V, X, and W), encoded by the CTSK gene in humans^1,2

Major cellular sources: Osteoclasts, smooth muscle cells, macrophages, osteoblasts, and osteocytes^2,4

Disease states associated with: Inflammatory disorders, rheumatoid arthritis, osteoarthritis, osteoporosis, and pycnodysostosis^2,4

Major physiologic functions:

• CTSK is highly and selectively expressed in osteoclasts, where it is involved in bone remodeling and resorption.^2,3,5
• Within osteoclasts, CTSK has been shown to reside in lysosomes and cytoplasmic vesicles and along the osteoclast-bone resorptive interface, and CTSK processing and activation in vivo occurs intracellularly.⁴
• CTSK expression is mediated by RANKL-induced activation of the transcription factor NFATc1, which targets the CTSK promoter. Factors such as IFN- , calcitonin, and estrogen reduce CTSK mRNA and protein expression.⁴
• CTSK is of crucial importance for the efficient degradation of collagen types I and II and can also degrade aggrecan, elastin, and osteonectin/SPARC.2 Upregulation or elevated levels of CTSK are associated with osteoarthritis, osteoporosis, and a wide range of cardiopathies.^1,2
• The absence of CTSK activity in humans results in pycnodysostosis, characterized by increased bone mineral density and fractures.⁴

CTSO: cathepsin O; IFN- : interferon gamma; mRNA: messenger ribonucleic acid; NFATc1: nuclear factor of activated T cells, cytoplasmic 1; PKND: protein kinase D; RANKL: receptor activator of nuclear factor-kappa B ligand; SPARC: secreted protein acidic and rich in cysteine.