Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages

Abstract

Background: Osteoarthritis (OA) is a common joint disorder worldwide which causes great health and economic burden. However, there remains an unmet goal to develop an effective therapeutic method to prevent or delay OA. Chondrocytes, as the major cells involved in OA progression, may serve as a promising therapeutic target. Results: A kind of carbon dots (CDs) with excellent biocompatibility was fabricated from folic acid via hydrothermal method and could effectively attenuate osteoarthritis. It was demonstrated that CDs treatment could rescue IL1β-induced proinflammatory responses, oxidative stress, cartilage degeneration and extracellular matrix degradation. Moreover, CDs reprogrammed lipopolysaccharide (LPS)-induced macrophage inflammation and polarization. Conditioned medium (CM) from CDs-treated macrophages could attenuate IL1β-induced chondrocyte injury. Also, CM from CDs-treated chondrocytes had immunoregulatory functions on macrophages. Mechanistically, CDs inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in IL1β-stimulated chondrocytes. In vivo, anterior cruciate ligament transection (ACLT) mice model was adopted and it was indicated that intra-articular injection of CDs effectively delays OA pathogenesis. Conclusions: Taken together, these findings indicated CDs could mediate OA via promoting cartilage repair and immunomodulating macrophages within local microenvironment, which may provide evidences for utilizing CDs as a novel nanomaterial for OA treatment.