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 3months with either 100mg/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.
Highlights
Osteoarthritis (OA) has major joint and bone hallmarks, and is the most common cause of gait impairment and physical disability [1]
The importance of PC's is illustrated in Fig. 1A and indicates that 64.6% of the variation contained in the data are retained by the first three principal components and 81.1% in the first 5 PC's
Together these data indicate a significantly greater symmetry and synchronisation of movement and gait that is more rhythmic and less turbulent in SFX-01® compared with vehicle treated spontaneously osteoarthritic STR/Ort mice
Summary
Osteoarthritis (OA) has major joint and bone hallmarks, and is the most common cause of gait impairment and physical disability [1]. OA affects all facets of joint integrity, with thinning of the articular cartilage accompanied by subchondral bone thickening, along with formation of bony osteophytic projections [2]. The role of bone, especially the subchondral plate, in the initiation and progression of OA has been the subject of many studies [3,4,5,6]. Despite such improvement in our understanding of OA, effective treatment options remain limited. The significant socio-economic burden this creates, requires development of new disease-modifying drugs which effectively target OA changes in cartilage and bone
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