Possible chondroprotective effect of canakinumab: An in vitro study on human osteoarthritic chondrocytes

Abstract

chondro-induction). Chondro-induction was lower (1.3AE0.4) and less reproducible when coculture was performed with M14 and did not occur with skin fibroblasts. GAG contents of constructs generated by solely macrophages were undetectable. Histological analyses of constructs confirmed the biochemical results. In the coculture there was no modulation of the chondrogenic genes. As compared to monocultures, in co-culture MSC and M24 numbers decreased less markedly (at day 7, MSC were 84% and 42% of the initial number, M24 were 26% of the initial number and undetectable, respectively for co-cultured and monocultured cells). Conclusions: We have demonstrated that coculture MSC/M42 results in synergistic cartilage tissue formation, which is not mediated by soluble factors alone. Further studies are envisioned to investigate whether M42 modulate the survival of specific MSC sub-populations. Finally, in vivo studies are necessary to assess the clinical relevance of our findings in the context of cartilage repair. Purpose: Brazilin is one major constituent of Caesalpinia sappan and is known to possess anti-bacterial, anti-oxidative, and anti-inflammatory activities. Osteoarthritis (OA) creates a disequilibrium between the catabolic and anabolic activities of chondrocytes in remodeling the Abstracts / Osteoarthritis and Cartilage 22 (2014) S57-S489 S148

Mitochondrial Transplantation Ameliorates The Development and Progression of Osteoarthritis.

“…Mitochondrial dysfunction occurs during OA progression (8, 9) and manifests as decreased ATP synthesis, decreased membrane potential, and increased oxidative stress, resulting in cartilage destruction (39). Mitochondrial dysfunction induces IL-1b release and leads to in ammation in chondrocytes by decreasing respiratory chain complex activity (6, 40).…”

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

“…Canakinumab, a human mAb that neutralizes IL-1β, can significantly downregulate the expression of MMP-1, MMP-3, and MMP-13 in human OA chondrocytes induced by TNF-α and IL-1β by blocking IL-1β interaction with its receptor, exerting potential chondroprotective effects ( Cheleschi et al, 2015 ). In an exploratory clinical trial, canakinumab reduced the overall hip or knee arthroplasty rate in patients with a history of OA at baseline ( Schieker et al, 2020 ).…”

Prospects for Therapies in Osteoarthritis

“…However, there have been further developments in the use of IL-1 in treating OA, involving canakinumab, a monoclonal antibody targeting IL-1β. Previous in vitro studies of canakinumab on human chondrocytes demonstrated increased proteoglycan and reduced nitric oxide synthesis which may reduce cartilage breakdown [ 98 ]. Canakinumab was recently studied in the CANTOS trial: a very large randomised, placebo-controlled trial investigating the cardiovascular effect of subcutaneous canakinumab [ 99 ].…”