Osteoarthritis (OA) is a chronic debilitating joint disease, characterized by degeneration of the cartilage and loss of the cartilage matrix, and it is clinically manifested as joint pain. Osteopontin (OPN) is a glycoprotein that is abnormally expressed in the bone and cartilage tissues and plays a vital role in various pathological processes such as the osteoarthritic inflammatory response and endochondral ossification. The focus of our study is to investigate the therapeutic potential and specific role of OPN in OA. Using morphological comparisons, we found that the cartilage was severely worn-out and there was a significant loss of the cartilage matrix in OA. OPN, CD44, and hyaluronic acid (HA) synthase 1 (HAS1) were highly expressed, and the anabolism of HA was significantly higher in the OA chondrocytes than in the control chondrocytes. Additionally, we treated the OA chondrocytes with small interfering RNA (siRNA) targeting OPN, recombinant human OPN (rhOPN), and a combination of rhOPN and anti-CD44 antibodies. Furthermore, in vivo experiments were performed in mice. We found that OPN upregulated the expression of downstream HAS1 and increased the anabolism of HA through CD44 protein expression in OA mice compared with those in control mice. Moreover, intra-articular injection of OPN in mice with OA significantly inhibited OA progression. In summary, OPN initiates an intracellular cascade via CD44 which results in an anabolic increase in HA levels, thereby inhibiting OA progression. Therefore, OPN is a promising therapeutic agent in precision treatment of OA.

骨关节炎（OA）是一种慢性衰弱性关节疾病，以软骨变性和软骨基质丢失为特征，临床表现为关节疼痛。骨桥蛋白（OPN）是一种在骨和软骨组织中异常表达的糖蛋白，在骨关节炎炎症反应和软骨内骨化等多种病理过程中发挥着重要作用。我们研究的重点是研究 OPN 在 OA 中的治疗潜力和具体作用。通过形态学比较，我们发现骨关节炎中软骨严重磨损，软骨基质显着损失。OPN、CD44 和透明质酸 (HA) 合酶 1 (HAS1) 高表达，并且 OA 软骨细胞中 HA 的合成代谢显着高于对照软骨细胞。此外，我们还用靶向 OPN 的小干扰 RNA (siRNA)、重组人 OPN (rhOPN) 以及 rhOPN 和抗 CD44 抗体的组合处理 OA 软骨细胞。此外，在小鼠身上进行了体内实验。我们发现，与对照小鼠相比，OPN 上调了 OA 小鼠下游 HAS1 的表达，并通过 CD44 蛋白表达增加了 HA 的合成代谢。此外，给患有 OA 的小鼠关节内注射 OPN 可以显着抑制 OA 的进展。总之，OPN 通过 CD44 启动细胞内级联反应，导致 HA 水平合成代谢增加，从而抑制 OA 进展。因此，OPN是一种有前途的OA精准治疗药物。