Cathepsin K: The Action in and Beyond Bone

Rongchen Dai, Zeting Wu, Hang Yin Chu, Jun Lu, Aiping LYU, Jin LIU*, Ge ZHANG

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)

Abstract

Cathepsin K (CatK) is one of the most potent proteases in lysosomal cysteine proteases family, of which main function is to mediate bone resorption. Currently, CatK is among the most attractive targets for anti-osteoporosis drug development. Although many pharmaceutical companies are working on the development of selective inhibitors for CatK, there is no FDA approved drug till now. Odanacatib (ODN) developed by Merck & Co. is the only CatK inhibitor candidate which demonstrated high therapeutic efficacy in patients with postmenopausal osteoporosis in Phase III clinical trials. Unfortunately, the development of ODN was finally terminated due to the cardio-cerebrovascular adverse effects. Therefore, it arouses concerns on the undesirable CatK inhibition in non-bone sites. It is known that CatK has far-reaching actions throughout various organs besides bone. Many studies have also demonstrated the involvement of CatK in various diseases beyond the musculoskeletal system. This review not only summarized the functional roles of CatK in bone and beyond bone, but also discussed the potential relevance of the CatK action beyond bone to the adverse effects of inhibiting CatK in non-bone sites.

Original languageEnglish
Article number433
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - 4 Jun 2020

Scopus Subject Areas

  • Developmental Biology
  • Cell Biology

User-Defined Keywords

  • bone resorption
  • cardiovascular diseases
  • Cathepsin K
  • Cathepsin K inhibitor
  • lung fibrosis
  • osteoarthritis
  • osteoclast
  • osteoporosis

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