Unveiling the macrophage dynamics in osteoarthritic joints: From inflammation to therapeutic strategies.

Osteoarthritis (OA) is an incurable, painful, and debilitating joint disease affecting over 500 million people worldwide. The OA joint tissues are infiltrated by various immune cells, particularly macrophages, which are able to induce or perpetuate inflammation. Notably, synovitis and its macrophage component represent a target of interest for developing treatments. In this review, we describe the latest advances in understanding the heterogeneity of macrophage origins, phenotypes, and functions in the OA joint and the effect of current symptomatic therapies on these cells. We then highlight the therapeutic potential of anticytokines/chemokines, nano- and microdrug delivery, and future strategies to modulate macrophage functions in OA.

Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF.

BACKGROUND: Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. METHODS: Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays. RESULTS: We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF. CONCLUSION: These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis. Video Abstract.