Abstract: Abstract: Objective To observe the therapeutic effect of Salubrinal on non-uniform settlement of tibial plateau in early osteoarthritis of surgery-induced mouse model. Methods Thirty mice were randomly equally divided into sham operation group (Sham), osteoarthritis group (OA) and osteoarthritis + Salubrinal group (OA + Sal). The OA model was established using surgery-removed medial meniscus of the knee joint in mice. Mice of OA + Sal group were injected subcutaneously with Salubrinal (1 mg/kg) for two weeks, Sham group and OA group were treated with isodose normal saline. Safranin O and tartrate-resistant acid phosphatase (TRAP) staining were used to observe the changes of histomorphology and the osteoclast activity in medial and lateral tibia plateau. The ability of formation, migration and adhension of osteoclasts from bone marrow-derived cells were evaluated to detect the development of osteoclasts. Results Compared with Sham group, the osteoclast development was significantly activated in OA group, and the osteoclast activity of subchondral bone was also increased. The OARSI score of articular cartilage and the proportion of calcified cartilage (CC/TAC) were obviously elevated (P＜0.05) in OA group. Interestingly, the medial tibial plateau B.Ar/T.Ar was increased significantly (P＜0.05), but the B.Ar/T.Ar and SBP were decreased significantly at lateral tibial plateau (P＜0.05) in OA group. Compared with OA group, the osteoclast development and subchondral osteoclast activity were significantly inhibited in OA + Sal group (P＜ 0.05). The OARSI score and CC/TAC were decreased (P＜0.05) in OA+Sal group. Moreover, the non-uniform changes of B. Ar / T. Ar and SBP were recovered apparently in the subchondral bone of the medial and lateral tibial plateau (P＜0.05). Conclusion Salubrinal plays a significant role in bone remodeling and non-uniform settlement of tibial plateau at early stage of osteoarthritis through regulating osteoclast development.

Key words: osteoarthritis, subchondral bone, bone remodeling, osteoclast, non-uniform settlement, Salubrinal