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Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis

Louka, Polymnia; Orriss, Isabel R.; Pitsillides, Andrew A.

Authors

Polymnia Louka

Isabel R. Orriss

Andrew A. Pitsillides



Abstract

Sulforaphane, the native but unstable form of SFX-01, is an antioxidant that activates the NRF2 and inhibits the NF-KB pathways to achieve its actions. Resolving the mechanism(s) by which SFX-01 serves to control the various osteoclastogenic stages may expose pathways that could be explored for therapeutic use. Here we seek to identify the stage of osteoclastogenesis targeted by SFX-01 and explore whether, like SFN, it exerts its actions via the NRF2 and NF-KB pathways. Osteoclasts generated from the bone marrow (BM) of mice were cultured with SFX-01 at different timepoints to examine each phase of osteoclastogenesis separately. This showed that SFX-01 exerted actions throughout the process of osteoclastogenesis, but had its largest effects in the early osteoclast precursor differentiation stage. Thus, treatment with SFX-01 for the duration of culture, for the initial 3 days differentiation or for as little as the first 24 h was sufficient for effective inhibition. This aligned with data suggesting that SFX-01 reduced DC-STAMP levels, osteoclast nuclear number and modified cytoskeletal architecture. Pharmacological regulation of the NRF2 pathways, via selective inhibitors/activators, supported the anti-osteoclastogenic roles of an SFX-01-mediated by NRF2 activation, as well as the need for tight NF-KB pathway regulation in osteoclast formation/function.

Citation

Louka, P., Orriss, I. R., & Pitsillides, A. A. (2024). Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis. Cells, 13(2), https://doi.org/10.3390/cells13020165

Journal Article Type Article
Acceptance Date Jan 9, 2024
Online Publication Date Jan 16, 2024
Publication Date 2024
Deposit Date May 7, 2024
Publicly Available Date May 7, 2024
Print ISSN 2073-4409
Electronic ISSN 2073-4409
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 13
Issue 2
DOI https://doi.org/10.3390/cells13020165
Keywords sulforaphane; osteoclasts; osteoclastogenesis; NRF2 and NF-KB

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