Total joint arthroplasty (TJA) can effectively alleviate the pain caused by various joint diseases, and reconstruct the damaged joint function especially for the end-stage arthropathy. TJA is known as one of the most significant breakthroughs in orthopedics in the twentieth century. The long-term postoperative follow-up visits revealed a 20-year survival rate higher than 80% [1,2]. Many complications restrict the lifetime of the prosthesis implanted in TJA. At the same time, aseptic loosening induced by wear particles has been identified as the primary cause for postoperative failure, accounting for approximately 75% of revision cases . Over recent years, the number of patients with postoperative aseptic loosening has increased . There is no effective treatment method other than complicated revision surgery. The previous studies suggested that the biological reaction between periprosthetic tissues and wear particles induces chronic inflammation, which in turn brakes the bone metabolic balance and leads to periprosthetic osteolysis [5,6].
To clarify the effect of SR on osteoblast apoptosis, FITC fluorescence-labeled Annexin V and PI were used to double stain MC3T3-E1. The cells at different apoptosis stages were detected and classified by a flow cytometer (Figure 5A). The results demonstrated that the cell apoptosis rate of MC3T3-E1 with Ti CM co-culturing for 24 h increased from 4.33% ± 0.13% to 17.07% ± 0.60%. While the apoptosis rates of 0.5 and 1.0 mM SR groups were significantly decreased (13.77% ± 0.30% and 12.38% ± 0.48%, respectively; Figure 5B). The above outcomes showed that co-culturing with Ti CM might lead to osteoblast apoptosis, while application of 0.5 or 1.0 mM SR might significantly suppress the apoptosis and recover cell viability.
RANKL is known as a membrane protein secreted by osteoblasts, which could activate osteoclasts and facilitate bone resorption [46,47]. Besides, OPG is a decoy receptor to RANKL, which can compete with RANK to bind RANKL to inhibit osteoclastogenesis and bone resorption [48,49]. Osteoblasts secrete RANKL/OPG in a state of dynamic equilibrium, affected by microenvironment or cell stage. RANK/RANKL/OPG axis is a critical pathway to maintain the symbiotic relationship between bone resorption and bone formation [32,50]. In the present study, IHC staining results in mice showed that OPG positive cells in the SR group were increased, while RANKL positive cells were decreased. The expression and distribution of OPG and RANKL in osteoblasts were observed in vitro by using a multi-channel laser confocal microscope. A similar result was also found in mRNA expression of OPG and RANK in osteoblasts. The above in vivo and in vitro experiments proved that SR inhibits particle-induced osteolysis by regulating the expression of RANKL/OPG in osteoblasts. 2b1af7f3a8