Louka, P.; Orriss, I.R.; Pitsillides, A.A. Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis. Cells 2024, 13, 165, doi:10.3390/cells13020165.
Louka, P.; Orriss, I.R.; Pitsillides, A.A. Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis. Cells 2024, 13, 165, doi:10.3390/cells13020165.
Louka, P.; Orriss, I.R.; Pitsillides, A.A. Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis. Cells 2024, 13, 165, doi:10.3390/cells13020165.
Louka, P.; Orriss, I.R.; Pitsillides, A.A. Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis. Cells 2024, 13, 165, doi:10.3390/cells13020165.
Abstract
Sulforaphane, the native but unstable form of SFX-01, is an antioxidant that activates NRF2 and inhibits 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 hours 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 NRF2 pathways, via selective inhibitors/activators, supported anti-osteoclastogenic roles for an SFX-01-mediated by NRF2 activation, as well as a need for tight NF-KB pathway regulation in osteoclast formation/function.
Keywords
sulforaphane; osteoclasts; osteoclastogenesis; NRF2 and NF-KB
Subject
Biology and Life Sciences, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
