title: Cathepsin K preferentially solubilizes matured bone matrix.
abstract: Bone collagen undergoes a series of enzymatic and nonenzymatic posttranslational modifications with maturation. The aim of this study was to analyze the collagenolytic efficiency of cathepsin K in relation to the extent of bone collagen age. Bone collagen posttranslational maturation was induced in vitro by preincubating bovine fetal cortical bone specimens at 37 °C for different times. The collagen enzymatic cross-links pyridinoline (PYD) and deoxypyridinoline (DPD), the advanced glycation end product pentosidine (PEN), and the native (α) and β-isomerized C-telopeptide (CTX) isomers were measured in each bone specimen. After extraction, bone collagen was incubated with human recombinant cathepsin K at different concentrations and its collagenolytic activity was measured by the release of hydroxyproline. To assess the affinity of cathepsin K for isomerized and nonisomerized CTX isomers, incubation with cathepsin K was also performed in the presence of various concentrations of a specific inhibitor. We showed that preincubation of bone collagen at 37 °C induces a marked increase in the bone concentration of PYD, DPD, and PEN and of CTX isomerization as reflected by the ratio of α-/βCTX. This increase was associated with a parallel increase in the efficiency of cathepsin K to solubilize bone collagen. When cathepsin K was incubated in the presence of an inhibitor, the β-isomerized form of collagen from 3-month- and 8-year-old bovine bone was more susceptible to degradation than the native α form. These results suggest that the collagenolytic activity of cathepsin K may be increased toward more matured bone collagen.
authors.affiliation: INSERM Unit 1033, Hôpital Edouard Herriot, Pavillon F, 69437, Lyon Cedex 03, France. olivier.borel@inserm.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Borel
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gineyts
authors.forename: Cindy
authors.initials: C
authors.lastname: Bertholon
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015519:Bone Density; D001857:Bone Matrix / Q000378:metabolism*; D056657:Cathepsin K / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D010455:Peptides / Q000378:metabolism
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D001120:Arginine; C062187:pentosidine; C534130:CTSK protein, human; D056657:Cathepsin K; D008239:Lysine