Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter, randomized, double‐blind, placebo‐controlled study

Chevalier, Xavier; Goupille, Philippe; Beaulieu, André; Burch, Francis X.; Bensen, W.; Conrozier, Thierry; Lœuille, Damien; Kivitz, Alan; Silver, David; Appleton, Brent E.

doi:10.1002/art.24096

Cited by 465 publications

(345 citation statements)

References 68 publications

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“…Matrix protein fragments, including those from the major cartilage component collagen II, also depend on NF-κB to stimulate expression of MMPs, NO and inflammatory cytokines [69,70]. Since biologic agents that block either TNFα or IL-1β do not block OA progression [71,72], it is likely that other stimuli for NF-κB activation, in combination with non-cytokine transcriptional targets of NF-κB, cause significant cartilage destruction.…”

Section: Osteoarthritismentioning

confidence: 99%

Role of NF-κB in the skeleton

2010

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Since the discovery that deletion of the NF-κB subunits p50 and p52 causes osteopetrosis in mice, there has been considerable interest in the role of NF-κB signaling in bone. NF-κB controls the differentiation or activity of the major skeletal cell types -osteoclasts, osteoblasts, osteocytes and chondrocytes. However, with five NF-κB subunits and two distinct activation pathways, not all NF-κB signals lead to the same physiologic responses. In this review, we will describe the roles of various NF-κB proteins in basal bone homeostasis and disease states, and explore how NF-κB inhibition might be utilized therapeutically.

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Section: Osteoarthritismentioning

confidence: 99%

Role of NF-κB in the skeleton

2010

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“…A single intraarticular injection of recombinant IL-1Ra acutely following an anterior cruciate ligament (ACL) tear has been shown to improve joint function and decrease pain (28), but the recombinant protein has a short half-life within the joint. This strategy has not been as successful for primary OA treatment (29). IL-1Ra gene therapy, in which virus (30) or cells transduced ex vivo (31) are injected into the joint, has shown promise in animal models and has progressed to clinical trials, demonstrating the importance of IL-1 as a target in OA treatment and the potential of IL-1Ra as a therapeutic (reviewed in ref.…”

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confidence: 99%

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

Moutos

Glass

Compton

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

102

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Biological resurfacing of entire articular surfaces represents an important but challenging strategy for treatment of cartilage degeneration that occurs in osteoarthritis. Not only does this approach require anatomically sized and functional engineered cartilage, but the inflammatory environment within an arthritic joint may also inhibit chondrogenesis and induce degradation of native and engineered cartilage. The goal of this study was to use adult stem cells to engineer anatomically shaped, functional cartilage constructs capable of tunable and inducible expression of antiinflammatory molecules, specifically IL-1 receptor antagonist (IL-1Ra). Large (22-mm-diameter) hemispherical scaffolds were fabricated from 3D woven poly(ε-caprolactone) (PCL) fibers into two different configurations and seeded with human adipose-derived stem cells (ASCs). Doxycycline (dox)-inducible lentiviral vectors containing eGFP or IL-1Ra transgenes were immobilized to the PCL to transduce ASCs upon seeding, and constructs were cultured in chondrogenic conditions for 28 d. Constructs showed biomimetic cartilage properties and uniform tissue growth while maintaining their anatomic shape throughout culture. IL-1Ra–expressing constructs produced nearly 1 µg/mL of IL-1Ra upon controlled induction with dox. Treatment with IL-1 significantly increased matrix metalloprotease activity in the conditioned media of eGFP-expressing constructs but not in IL-1Ra–expressing constructs. Our findings show that advanced textile manufacturing combined with scaffold-mediated gene delivery can be used to tissue engineer large anatomically shaped cartilage constructs that possess controlled delivery of anticytokine therapy. Importantly, these cartilage constructs have the potential to provide mechanical functionality immediately upon implantation, as they will need to replace a majority, if not the entire joint surface to restore function.

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“…94,95 However, no significant improvement in symptoms was observed following intra-articular injection of a recombinant form of IL-1-receptor antagonist (IL-1RA) to patients with knee OA. 96 It appears that the potential of current antiinflammatory therapies to improve structural damage is limited, and the development of novel immune modulation strategies is required to alter the progression of OA.…”

Section: Infiltrating Cd3mentioning

confidence: 99%