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Cathepsin K Preferentially Solubilizes Matured Bone Matrix

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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.

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Acknowledgements

We thank Dr. Jean Marie Délaissé for helpful discussion.

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Authors and Affiliations

  1. INSERM Unit 1033, Hôpital Edouard Herriot, Pavillon F, 69437, Lyon Cedex 03, France

    Olivier Borel, Evelyne Gineyts, Cindy Bertholon & Patrick Garnero

  2. Cisbio Bioassays, Parc Marcel Boiteux, P. O. Box 84175, 30200, Codolet, France

    Patrick Garnero

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  1. Olivier Borel
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  2. Evelyne Gineyts
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  4. Patrick Garnero
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Correspondence to Olivier Borel.

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Borel, O., Gineyts, E., Bertholon, C. et al. Cathepsin K Preferentially Solubilizes Matured Bone Matrix. Calcif Tissue Int 91, 32–39 (2012). https://doi.org/10.1007/s00223-012-9604-7

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  • DOI: https://doi.org/10.1007/s00223-012-9604-7

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