METHODS: 20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA.
RESULTS: There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system.
CONCLUSION: The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.
STATEMENT OF SIGNIFICANCE: In this study, we developed a silk scaffold with increased stiffness and SDF-1 controlled release capacity for ligament repair. This advanced scaffold transplantation combined with intra-articular injection of LSPCs (which was isolated from rabbit ligament for the first time in this study) promoted the regeneration of both the tendinous and bone tunnel portion of ACL. This therapeutic strategy also ameliorated cartilage degeneration and reduced the severity of arthrofibrosis. Hence, combining LSPCs injection with SDF-1-releasing silk scaffold is demonstrated as a therapeutic strategy for ACL regeneration and OA treatment in the clinic.