Sulfasalazine attenuates ACL transection and medial menisectomy‐induced cartilage destruction by inhibition of cystine/glutamate antiporter

Abstract

We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system X À C ) expression. System X À C uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system X À C in OA is rarely addressed. Sulfasalazine (SSZ) is a system X À C inhibitor; SSZ was applied intra-articularly to study the function of system X À C in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT þ MMx). Moerover, the system X À C activator N-acetylcysteine (NAC) was also applied to verify the role of system X À C . The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT þ MMx rats and this effect was blocked by NAC. The results showed that inhibition of system X À C function can attenuate ACLT þ MMx-induced cartilage destruction. In the present study, system X À C inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT þ MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ. ß

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…Following the previous reports, OA was induced in rats [ 47 , 48 , 49 ]. The ACLT + MMx method was employed to induce OA in rats, and surgery on the right knee joint was performed ( Figure 2 ).…”

Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases

“…Tsai et al have investigated the action of Sxc- in the onset of knee osteoarthritis (OA) in rats after anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). They have observed that the intra-articular application of SSZ reduced knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this action was blocked by NAC [130]. Nishio et al have observed the actions of ROS on synaptic transmission in rat spinal cord substantia gelatinosa (SG) neurons using whole-cell patch-clamp recordings.…”

Association of anterior cruciate ligament injury with knee osteoarthritis and total knee replacement: A retrospective cohort study from the Taiwan National Health Insurance Database

“…Such an analysis may provide new strategies for the future management of knee conditions, particularly early management of knee injuries. As demonstrated in our previous serial studies using an ACL transaction and partial medial meniscectomy rat model, early medical intervention delays OA development [46–48]. These findings may provide a new strategy for the early management of knee injuries that may reduce the disease burden, lower the incidence of knee arthroplasty and reduce NHI expenses.…”