From the lung to the knee joint: Toxicity evaluation of carbon black nanoparticles on macrophages and chondrocytes

Carbon black (CB), a core elemental carbon component of airborne particles, has been used as a model material to study environmental safety and health impacts of airborne particles. Although potential adverse effects of CB have been reported, limited knowledge is available regarding CB-induced metabolic disorders and secondary effects distant from primary target organs, such as the effects on joints. The knee cavity is a relatively closed space along the peripheral circulation route with a slow rate of interchange of nutrition with blood. While epidemiologic studies have indicated that airborne particle exposure may affect the occurrence and severity of inflammatory knee diseases, no research has been performed to understand the potential hazardous direct/indirect interactions between particles and knee cells. Herein, we have scrutinized the toxicity of four commercial nano-sized CB samples in the lung and a distant site: knee joint. Our results indicated that CB triggered pulmonary and systemic inflammation upon inhalation exposure, and, more strikingly, CB also elicited injuries of the knee joint, as demonstrated by thickened synovial membrane, suggesting disordered cellular metabolism within the knee joint. Our data recognized the CB toxicity profiles to macrophages as characterized by pro-inflammatory reactions, and also defined an activated metabolic state of chondrocytes, as evidenced by metalloproteinase (MMP) induction. Of note, remarkable variations were also found for these changes induced by these four CB samples, due to their distinct physicochemical properties. Collectively, our results uncovered a significant toxicity of CB inhalation exposure to the knee joint, as reflected by metabolic activation of chondrocytes, and, more importantly, these findings unearthed CB-induced metabolic disorders and secondary effects owing to systemic pro-inflammatory conditions upon CB exposure, in addition to the likelihood of direct toxicity to knee cells.