A cytochemical assay for osteoclast cathepsin K activity.
Cathepsin K is a member of the papain superfamily of cysteine proteases and plays a pivotal role in osteoclast-mediated bone resorption. This enzyme is an excellent target for antiresorptive therapies for osteopenic disorders such as osteoporosis.(1) Although isolated inhibitor studies on purified enzymes is required to discover potent and selective inhibitors of cathepsin K, a quantitative cytochemical assay(2) for cathepsin K would allow inhibitors to be tested on actual osteoclasts within sections of bone. Furthermore cathepsin K activity could be used to identify and analyse osteoclasts at definitive stages of their lifespan. A cytochemical assay is described that localizes osteoclast cathepsin K activity in unfixed, undecalcified cryostat sections of animal and human bone.
Dodds
Robert A
RA
Growth Factors Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, Raritan, NJ 08869, USA. RDoddds@prdus.jnj.com
D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology; D001842:Bone and Bones / Q000201:enzymology; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D010010:Osteoclasts / Q000737:chemistry / Q000201:enzymology*; D051381:Rats; D012680:Sensitivity and Specificity; D013379:Substrate Specificity
D004151:Dipeptides; D005456:Fluorescent Dyes; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534133:Ctsk protein, rat