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

Javaheri, B and Poulet, B and Aljazzar, A and De Souza, R and Piles, M and Hopkinson, M and Shervill, E and Pollard, A S and Chan, B and Chang, Y M and Orriss, I and Lee, P and Pitsillides, A A (2017) Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis. BONE, 103. pp. 308-317.

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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.