The Runt-related transcription factor (Runx) family plays various roles in the homeostasis of cartilage. Here, we examined the role of Runx2 and Runx3 for osteoarthritis development in vivo and in vitro. Runx3-knockout mice exhibited accelerated osteoarthritis following surgical induction, accompanied by decreased expression of lubricin and aggrecan. Meanwhile, Runx2 conditional knockout mice showed biphasic phenotypes: heterozygous knockout inhibited osteoarthritis and decreased matrix metallopeptidase 13 (Mmp13) expression, while homozygous knockout of Runx2 accelerated osteoarthritis and reduced type II collagen (Col2a1) expression. Comprehensive transcriptional analyses revealed lubricin and aggrecan as transcriptional target genes of Runx3, and indicated that Runx2 sustained Col2a1 expression through an intron 6 enhancer when Sox9 was decreased. Intra-articular administration of Runx3 adenovirus ameliorated development of surgically induced osteoarthritis. Runx3 protects adult articular cartilage through extracellular matrix protein production under normal conditions, while Runx2 exerts both catabolic and anabolic effects under the inflammatory condition.

Runt 相关转录因子 (Runx) 家族在软骨稳态中起着多种作用。在这里，我们检查了 Runx2 和 Runx3 在体内和体外对骨关节炎发展的作用。Runx3敲除小鼠在手术诱导后表现出加速的骨关节炎，并伴有润滑素和聚集蛋白聚糖的表达降低。同时，Runx2条件性敲除小鼠表现出双相表型：杂合子敲除抑制骨关节炎并降低基质金属肽酶 13 (Mmp13) 表达，而纯合子敲除Runx2加速骨关节炎和减少 II 型胶原 (Col2a1) 表达。综合转录分析显示润滑素和聚集蛋白聚糖是 Runx3 的转录靶基因，并表明当 Sox9 减少时，Runx2 通过内含子 6 增强子维持Col2a1表达。Runx3 腺病毒的关节内给药改善了手术诱发的骨关节炎的发展。Runx3 在正常条件下通过细胞外基质蛋白的产生来保护成人关节软骨，而 Runx2 在炎症条件下发挥分解代谢和合成代谢作用。