Investigation of osteoclast cathepsin K activity in osteoclastogenesis and bone loss using a set of chemical reagents.

Tomasz Janiszewski, Sonia Kołt, Izabela Ciastoń, Matej Vizovisek, Marcin Poręba, Boris Turk, Marcin Drąg, Joanna Kozieł, Paulina Kasperkiewicz

Cell chemical biology 2023 Feb 16

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Cathepsin K (CatK) is a lysosomal cysteine protease whose highest expression is found in osteoclasts, which are the cells responsible for bone resorption. Investigations of the functions and physiological relevance of CatK have often relied on antibody-related techniques, which makes studying its activity patterns a challenging task. Hence, we developed a set of chemical tools for the investigation of CatK activity. We show that our probe is a valuable tool for monitoring the proteolytic activation of CatK during osteoclast formation. Moreover, we demonstrate that our inhibitor of CatK impedes osteoclastogenesis and bone resorption and that CatK is stored in its active form in osteoclasts within their lysosomal compartment and mainly in the ruffled borders of osteoclasts. Given that our probe recognizes active CatK within living cells without exhibiting any observed cytotoxicity in the several models tested, we expect that it would be well suited to theranostic applications in CatK-related diseases. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Tomasz Janiszewski, Sonia Kołt, Izabela Ciastoń, Matej Vizovisek, Marcin Poręba, Boris Turk, Marcin Drąg, Joanna Kozieł, Paulina Kasperkiewicz. Investigation of osteoclast cathepsin K activity in osteoclastogenesis and bone loss using a set of chemical reagents. Cell chemical biology. 2023 Feb 16;30(2):159-174.e8