Runt-related transcription factor-1 (Runx1) is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development. However, the potential role of Runx1 in joint diseases is not well known. In the current study, we aimed to explore the role of Runx1 in osteoarthritis induced by anterior cruciate ligament transaction (ACLT) surgery. We showed that chondrocyte-specific Runx1 knockout (Runx1^f/fCol2a1-Cre) aggravated cartilage destruction by accelerating the loss of proteoglycan and collagen II in early osteoarthritis. Moreover, we observed thinning and ossification of the growth plate, a decrease in chondrocyte proliferative capacity and the loss of bone matrix around the growth plate in late osteoarthritis. We overexpressed Runx1 by adeno-associated virus (AAV) in articular cartilage and identified its protective effect by slowing the destruction of osteoarthritis in cartilage in early osteoarthritis and alleviating the pathological progression of growth plate cartilage in late osteoarthritis. ChIP-seq analysis identified new targets that interacted with Runx1 in cartilage pathology, and we confirmed the direct interactions of these factors with Runx1 by ChIP-qPCR. This study helps us to understand the function of Runx1 in osteoarthritis and provides new clues for targeted osteoarthritis therapy.

Runt 相关转录因子-1 (Runx1) 是软骨细胞到成骨细胞谱系承诺所必需的，通过在脊椎动物发育过程中增强软骨形成和成骨。然而，Runx1 在关节疾病中的潜在作用尚不清楚。在目前的研究中，我们旨在探讨 Runx1 在前交叉韧带置换 (ACLT) 手术诱导的骨关节炎中的作用。我们发现软骨细胞特异性 Runx1 敲除 ( Runx1 ^f/f Col2a1-Cre) 通过加速早期骨关节炎中蛋白多糖和胶原蛋白 II 的损失，加剧了软骨破坏。此外，我们观察到生长板变薄和骨化，软骨细胞增殖能力下降，晚期骨关节炎生长板周围骨基质丢失。我们通过关节软骨中的腺相关病毒 (AAV) 过表达 Runx1，并通过减缓早期骨关节炎中软骨中骨关节炎的破坏和减轻晚期骨关节炎中生长板软骨的病理进展来确定其保护作用。ChIP-seq 分析确定了在软骨病理学中与 Runx1 相互作用的新靶点，我们通过 ChIP-qPCR 证实了这些因素与 Runx1 的直接相互作用。