SUMO1 mediated salubrinal-treated the abnormal remodeling of the subchondral bone in osteoarthritis

Abstract

Abstract Background: Osteoarthritis (OA) is the most common joint disorder characterized by cartilage degradation and abnormal subchondral bone remodeling. As a post-translational modification, small ubiquitin-like modifiers (SUMOs) are involved in the pathogenesis of many diseases including arthritis. However, their role in OA remains to be elucidated. Furthermore, although salubrinal is reported to inhibit bone resorption and stimulate bone formation in osteoporosis, its effect on OA is not well understood. Methods: To elucidate the role of salubrinal in OA and any linkage to SUMOylation, 54 mice were employed in 3 randomly assigned groups (n = 18), including the sham control (control), osteoarthritis (OA), and salubrinal-treated OA (OAS). OA was induced by transecting the medial collateral ligament and removing the medial meniscus. Salubrinal was administered subcutaneously at a dose of 2mg/kg daily for 2 weeks. Results: Salubrinal reduced the osteoclast surface and elevated the osteoblast number in the trabecular subchondral bone. It also suppressed osteoclast activities and promoted osteoblast differentiation from bone marrow-derived cells. HE staining and CT imaging revealed that salubrinal improved the microstructure of the subchondral bone, and it reduced OARSI scores and CC/TAC. Silencing SUMO1 attenuated salubrinal’s beneficial effects on osteoclastogenesis and osteoblastogenesis. Conclusions: Salubrinal improved the abnormal remodeling of the subchondral bone in OA, and its beneficial effects were partly mediated by SUMO1.