The progression of osteoarthritis is associated with inflammation triggered by the enzymatic degradation of extracellular matrix in injured cartilage. Here we show that a locally injected depot of nanoparticles functionalized with an antibody targeting type II collagen and carrying small interfering RNA targeting the matrix metalloproteinase 13 gene (Mmp13), which breaks down type II collagen, substantially reduced the expression of MMP13 and protected cartilage integrity and overall joint structure in acute and severe mouse models of post-traumatic osteoarthritis. MMP13 inhibition suppressed clusters of genes associated with tissue restructuring, angiogenesis, innate immune responses and proteolysis. We also show that intra-articular injections of the nanoparticles led to greater reductions in disease progression than either a single injection or weekly injections of the steroid methylprednisolone. Sustained drug retention by targeting collagen in the damaged extracellular matrix of osteoarthritic cartilage may also be an effective strategy for the treatment of osteoarthritis with other disease-modifying drugs.

骨关节炎的进展与损伤软骨中细胞外基质的酶促降解引发的炎症有关。在这里，我们展示了局部注射的纳米颗粒库，该纳米颗粒用靶向 II 型胶原蛋白的抗体功能化并携带靶向基质金属蛋白酶 13 基因的小干扰 RNA ( Mmp13)，它可以分解 II 型胶原蛋白，显着降低 MMP13 的表达，并在急性和严重的创伤后骨关节炎小鼠模型中保护软骨完整性和整体关节结构。MMP13 抑制抑制了与组织重组、血管生成、先天免疫反应和蛋白水解相关的基因簇。我们还表明，与单次注射或每周注射类固醇甲基泼尼松龙相比，纳米颗粒的关节内注射可更大程度地减少疾病进展。通过靶向骨关节炎软骨受损细胞外基质中的胶原蛋白来持续药物保留，也可能是与其他疾病修饰药物一起治疗骨关节炎的有效策略。