Inhibition of Cysteine Protease Disturbs the Topological Relationship Between Bone Resorption and Formation in Vitro

Overview

Journal J Bone Miner Metab

Specialty Endocrinology

Date 2024 Feb 20

PMID 38376670

Authors

Sayaka Ono

Naoki Tsuji

Tomoaki Sakamoto

Shuya Oguchi

Takashi Nakamura

Kazuto Hoshi

Atsuhiko Hikita

Affiliations

Soon will be listed here.

Abstract

Introduction: Osteoporosis is a global health issue. Bisphosphonates that are commonly used to treat osteoporosis suppress both bone resorption and subsequent bone formation. Inhibition of cathepsin K, a cysteine proteinase secreted by osteoclasts, was reported to suppress bone resorption while preserving or increasing bone formation. Analyses of the different effects of antiresorptive reagents such as bisphosphonates and cysteine proteinase inhibitors will contribute to the understanding of the mechanisms underlying bone remodeling.

Materials And Methods: Our team has developed an in vitro system in which bone remodeling can be temporally observed at the cellular level by 2-photon microscopy. We used this system in the present study to examine the effects of the cysteine proteinase inhibitor E-64 and those of zoledronic acid on bone remodeling.

Results: In the control group, the amount of the reduction and the increase in the matrix were correlated in each region of interest, indicating the topological and quantitative coordination of bone resorption and formation. Parameters for osteoblasts, osteoclasts, and matrix resorption/formation were also correlated. E-64 disrupted the correlation between resorption and formation by potentially inhibiting the emergence of spherical osteoblasts, which are speculated to be reversal cells in the resorption sites.

Conclusion: These new findings help clarify coupling mechanisms and will contribute to the development of new drugs for osteoporosis.

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