Title : Intra-articular injection of kartogenin-conjugated nanomaterials for relieving osteoarthritis in rats
Abstract:
Background: Osteoarthritis is a common degenerative condition involving the cartilage and surrounding bones, with significant negative impact on quality of life and increased risk of physical disability. The kartogenin is a small molecule that has been previously shown to alleviate cartilage degeneration and possess protective efficacy. In this experimental study, we developed a chitosan nanoparticles loaded with kartogenin and assessed its efficacy to attenuate osteoarthritis in a rat model.
Methods: The kartogenin-conjugated nanoparticles were synthesized and characterized. Primary chondrocytes from rats were isolated, cultured, and subject to cytotoxicity assays with the CCK-8 assay. Moreover, supernatant pro-inflammatory cytokine concentration measurement was performed with the enzyme-linked immunosorbent assay. Rat osteoarthritis model was established by anterior cruciate ligament transection and destabilization of the medial meniscus. The efficacy of kartogenin-conjugated nanoparticles were assessed by creating 4 groups (n=6): control group (saline injection), chitosan group (chitosan injection), kartogenin group (kartogenin group), and kartogenin-chitosan group (kartogenin-chitosan injection). Cartilage damage by histology was semiquantitatively assessed using the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system.
Results: The kartogenin-chitosan nanoparticle is spherical in shape and measures approximately 25nm in size. CCK-8 test indicated that the kartogenin-chitosan nanoparticle had no cytotoxic effect on the chondrocytes and did not induce an elevation in pro-inflammatory cytokines interleukin-1, interleukin-6, interleukin-15 and tumor necrosis factor. In vivo studies in rat osteoarthritis indicated that the OARSI in the kartogenin-chitosan group was significantly lower than that in other groups since week 9.
Conclusion: This animal study suggested that kartogenin-conjugated chitosan nanoparticles are promising for the treatment of osteoarthritis that warrants further investigations in clinical trials.