Intra-articular injection of inorganic pyrophosphate improves IL-1β-induced cartilage damage in rat model of knee osteoarthritis in vivo.

Objective: Osteoarthritis (OA) is the most common form of chronic joint disease, affecting mainly the elderly population. This disorder is caused by cartilage degeneration with complex changes in the chondrocyte phenotype. Inorganic pyrophosphate (PPi) was shown to counteract the detrimental effect of interleukin (IL)-1β challenging in an in vitro OA model based on rat articular chondrocytes. It also maintained the differentiated articular phenotype, mostly by down regulating wingless-related integration site (Wnt)-5a secretion. These observations suggest a PPi protective role for chondrocyte in vitro. Methods: To address this hypothesis in vivo, we investigated the impact on knee joint of three intra-articular injection (IAI) of PPi in a rat model of cartilage damage induced by IAI of IL-1β, where cartilage degradation and synovial inflammation are similar to that observed in OA. Cartilage and synovial membrane were collected after 7 days of challenge by IL-1β. Results: PPi was able to reduce the deleterious effect of IL-1β. This effect was observable on the expression of cartilage extracellular matrix metabolism markers and confirmed by histology with safranin O and hematoxylin-eosin-saffron (HES) staining. Inorganic pyrophosphate also repressed the Wnt5a expression induced by IL-1β. No effect was observed on the inflammatory response of the synovial membrane. Conclusion: These results demonstrate that PPi improves IL-1β-induced cartilage damage in rat but not the associated inflammation of synovial membrane. Thus, PPi could become a molecule of interest to restrict the progression of this disorder.