Elucidating the mechano-molecular dynamics of TRAP activity using CRISPR/Cas9 mediated fluorescent reporter mice.

Autor:	Yılmaz D; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Marques FC; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Fischer Y; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Zimmermann S; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Hwang G; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Atkins PR; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.; Department of Orthopaedics, University of Utah, 590 Wakara Way, Salt Lake City, USA., Mathavan N; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Singh A; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., de Souza PPC; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.; Innovation in Biomaterials Laboratory, School of Dentistry, Federal University of Goiás, Goiânia, Brazil., Kuhn GA; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland., Wehrle E; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.; AO Research Institute Davos, Davos Platz, Switzerland., Müller R; Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Jun 13; Vol. 10 (12), pp. e32949. Date of Electronic Publication: 2024 Jun 13 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e32949
Abstrakt:	Osteoclasts are essential for bone remodeling by adapting their resorptive activity in response to their mechanical in vivo environment. However, the molecular mechanisms underlying this process remain unclear. Here, we demonstrated the role of tartrate-resistant acid phosphatase (TRAP, Acp5), a key enzyme secreted by osteoclasts, in bone remodeling and mechanosensitivity. Using CRISPR/Cas9 reporter mice, we demonstrated bone cell reporter (BCR Ibsp/Acp5 ) mice feature fluorescent TRAP-deficient osteoclasts and examined their activity during mechanically driven trabecular bone remodeling. Although BCR Ibsp/Acp5 mice exhibited trabecular bone impairments and reduced resorption capacity in vitro , RNA sequencing revealed unchanged levels of key osteoclast-associated genes such as C tsk, Mmp9, and Calcr . These findings, in conjunction with serum carboxy-terminal collagen crosslinks (CTX) and in vivo mechanical loading outcomes collectively indicated an unaltered bone resorption capacity of osteoclasts in vivo . Furthermore, we demonstrated similar mechanoregulation during trabecular bone remodeling in BCR Ibsp/Acp5 and wild-type (WT) mice. Hence, this study provides valuable insights into the dynamics of TRAP activity in the context of bone remodeling and mechanosensation. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Ralph Mueller reports financial support was provided by 10.13039/501100000781European Research Council and Prof. Pedro P.C. de Souza reports that he was financed by the ERC/CONFAP/CNPq grant. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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