Mutations in the cathepsin K gene are associated with pycnodysostosis, a hereditary osteopetrotic disease, characterised by a lack of functional cathepsin K expression. Knockout studies of cathepsin K in mice lead to an osteopetrotic phenotype, which, is partially compensated by increased expression of proteases other that cathepsin K and enhanced osteoclastogenesis. Cathepsin K has an optimal enzymatic activity in acidic conditions. It is synthesized as a proenzyme with a molecular weight of 37kDa, and upon activation by autocatalytic cleavage, is transformed into the mature, active form with a molecular weight of ~27kDa. Upon polarization of the osteoclast over the site of resorption, cathepsin K is secreted from the ruffled border into the resorptive pit. Cathepsin K transmigrates across the ruffled border by intercellular vesicles and is then released by the functional secretory domain. Within these intercellular vesicles, cathepsin K, along with reactive oxygen species generated by TRAP, further degrades the bone extracellular matrix. Several other cathepsins are expressed in osteoclasts including cathepsins B, C, D, E, G, and L.  The function of these cysteine and aspartic proteases is generally unknown within bone, and they are expressed at much lower levels than cathepsin K.
Studies on cathepsin L knockout mice have been mixed, with a report of reduced trabecular bone in homozygous and heterozygous cathepsin L knockout mice compared to wild-type and another report finding no skeletal abnormalities. Matrix metalloproteinases
The matrix metalloproteinases (MMPs) comprise a family of more than 20 zinc-dependent endopeptidases.
Clinical significance
Giant osteoclasts can occur in some diseases, including Pagets disease of bone and bisphosphonate toxicity. In cats, abnormal odontoclast activity can cause feline odontoclastic resorptive lesions, necessitating extraction of the affected teeth. History
Osteoclasts were discovered by Kolliker in 1873. See also
List of human cell types derived from the germ layers

References
External links
MedicineNet
Osteoclasts at the US National Library of Medicine Medical Subject Headings (MeSH)
The Life of Osteoclast
Random42: Animation by Random42 Scientific Communication on the role of osteoclasts in bone remodeling