Autologous protein solution inhibits MMP‐13 production by IL‐1β and TNFα‐stimulated human articular chondrocytes

Abstract

Catabolic inflammatory cytokines are prevalent in osteoarthritis (OA). The purpose of this study was to evaluate an autologous protein solution (APS) as a potential chondroprotective agent for OA therapy. APS was prepared from platelet-rich plasma (PRP). The APS solution contained both anabolic (bFGF, TGF-b1, TGF-b2, EGF, IGF-1, PDGF-AB, PDGF-BB, and VEGF) and antiinflammatory (IL-1ra, sTNF-RI, sTNF-RII, IL-4, IL-10, IL-13, and IFNg) cytokines but low concentrations of catabolic cytokines (IL-1a, IL-1b, TNFa, IL-6, IL-8, IL-17, and IL-18). Human articular chondrocytes were pre-incubated with the antagonists IL-1ra, sTNF-RI, or APS prior to the addition of recombinant human IL-1b or TNFa. Following exposure to inflammatory cytokines, the levels of MMP-13 in the culture medium were evaluated by ELISA. MMP-13 production stimulated in chondrocytes by IL-1b or TNFa was reduced by rhIL-1ra and sTNF-RI to near basal levels. APS was also capable of inhibiting the production of MMP-13 induced by both IL-1b and TNFa. The combination of anabolic and anti-inflammatory cytokines in the APS created from PRP may render this formulation to be a potential candidate for the treatment of inflammation in patients at early stages of OA. ß

Thymoquinone Inhibits IL-1β-Induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing NF-κB and MAPKs Signaling Pathway

“…These inflammatory mediators amplified the inflammation and play important roles in the pathophysiology of OA. Furthermore, IL-1β also induced the release of catabolic enzymes, such as MMP-1, MMP-3, and MMP-13 [20]. These catabolic enzymes have the ability to excess cartilage matrix degradation in OA [21].…”

Blood-derived anti-inflammatory protein solution blocks the effect of IL-1β on human macrophages in vitro

“…This is because APS contains concentrated levels of anti-inflammatory cytokines other than IL-1ra, including sTNF-RI. A comprehensive characterization of APS has been performed, and the concentration of multiple anti-inflammatory cytokines and growth factors provides multiple avenues for the blockade of inflammatory agents [29]. This anti-inflammatory combination results in a synergistic effect, thereby requiring less of each protein to produce an effective blockade of inflammation.…”

“…This was necessary to prevent a human leukocyte antigen reaction between the two cell populations. A study using APS to treat human chondrocytes (NHAC-kn) was performed in parallel to this one and did not require the lysis of APS cells prior to treatment [29]. This was because chondrocytes are not professional antigen-presenting cells and do not produce the averse immune response that macrophages do.…”

Clinical Aspects of Regenerative Medicine

“…Ideologically, a PRP cocktail for OA would be more anti-inflammatory with less pro-inflammatory cytokines. Future research aims to isolate cytokines contained in PRP to specifically inhibit IL-1 and TNF alpha and downregulate MMP-13 [57].…”