ECTS Abstracts (2015) 1 P14

A stable synthetic sulforaphane significantly improves bone architecture and gait in the naturally occurring str/ort model of osteoarthritis

Behzad Javaheri1, Blandine Poulet2, Ahmad Aljazzar1, Yu-Mei Chang1, Roberto De Souza1, Mark Hopkinson1 & Andrew Pitsillides1

1The Royal Veterinary College, London, UK; 2University College London, London, UK.

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in preventing/ reversing such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant inflammation modulator. Herein, we explore whether Sulforadex, 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 Sulforadex or vehicle (0.5% sodium carboxymethyl cellulose in H2O). Gait was recorded and analysed using a DigiGait imaging system. Tibiae were microCT scanned using a Skyscan 1172 and architecture in a defined trabecular bone region and the entire cortical shaft analysed. Right knees were decalcified, wax-embedded and multiple 6 μm coronal sections collected from across each entire joint stained with toluidine blue. OA lesion severity was graded using an Internationally recognised system. Analysis revealed development of asymmetric gait (hind limb paw area), normally linked to OA, in vehicle-treated Str/ort mice, which did not emerge in Sulforadex-treated mice. Fore-limb asymmetry followed similar patterns. We found significantly increased trabecular bone volume/total volume, bone surface and trabecular number in Sulforadex-treated mice. This was consistent with significantly increased indices of bone strength (cross-sectional thickness, Imin/Imax in many regions along the tibial shaft. Despite these marked improvements in gait and superior trabecular and cortical bone mass and architecture, we found that histologically-graded OA severity in articular cartilage was unmodified in the Sulforadex-treated mice. This indicates that Sulforadex improves bone microarchitecture and indices of mechanical strength and produces greater symmetry in gait without any marked effects on cartilage lesion development in these spontaneously osteoarthritic mice. Our findings support novel osteotrophic roles for Sulforadex and beneficial gait effects that appear to be independent of articular cartilage lesion development in OA.

Disclosure: The authors declared no competing interests.

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