SPP1 and fibrosis: Briefly, IPFP‐derived OPN participates in OA progression, including chondrocyte hypertrophy and IPFP fibrosis, and intra‐IPFP injection of tailored RGD−Nanogel/siRNA Cd61 effectively arrests the cartilage erosion and IPFP inflammation, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass, leading to an innovative therapeutic strategy to mitigate OA progression.