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 (Runx1f/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.