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Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis

Javaheri, B; Poulet, B; Aljazzar, A; De Souza, R; Piles, M; Hopkinson, M; Shervill, E; Pollard, A S; Chan, B; Chang, Y M; Orriss, I; Lee, P; Pitsillides, A A

Authors

B Javaheri

B Poulet

A Aljazzar

R De Souza

M Piles

M Hopkinson

E Shervill

A S Pollard

B Chan

Y M Chang

I Orriss

P Lee

A A Pitsillides



Abstract

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Herein, we explore whether SFX-01®, a stable synthetic form of sulforaphane, modifies gait, bone architecture and slows/reverses articular cartilage destruction in a spontaneous OA model in STR/Ort mice. Sixteen mice (n = 8/group) were orally treated for 3 months with either 100 mg/kg SFX-01® or vehicle. Gait was recorded, tibiae were microCT scanned and analysed. OA lesion severity was graded histologically. The effect of SFX-01® on bone turnover markers in vivo was complemented by in vitro bone formation and resorption assays. Analysis revealed development of OA-related gait asymmetry in vehicle-treated STR/Ort mice, which did not emerge in SFX-01®-treated mice. We found significant improvements in trabecular and cortical bone. Despite these marked improvements, we found that histologically-graded OA severity in articular cartilage was unmodified in treated mice. These changes are also reflected in anabolic and anti-catabolic actions of SFX-01® treatment as reflected by alteration in serum markers as well as changes in primary osteoblast and osteoclast-like cells in vitro. We report that SFX-01® improves bone microarchitecture in vivo, produces corresponding changes in bone cell behaviour in vitro and leads to greater symmetry in gait, without marked effects on cartilage lesion severity in STR/Ort osteoarthritic mice. Our findings support both osteotrophic roles and novel beneficial gait effects for SFX-01® in this model of spontaneous OA.

Citation

Javaheri, B., Poulet, B., Aljazzar, A., De Souza, R., Piles, M., Hopkinson, M., …Pitsillides, A. A. (2017). Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis. BONE, 103, 308-317. https://doi.org/10.1016/j.bone.2017.07.028

Journal Article Type Article
Acceptance Date Jul 31, 2017
Publication Date Aug 1, 2017
Deposit Date Aug 10, 2017
Publicly Available Date Mar 29, 2024
Journal BONE
Print ISSN 8756-3282
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 103
Pages 308-317
DOI https://doi.org/10.1016/j.bone.2017.07.028
Public URL https://rvc-repository.worktribe.com/output/1391025

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