Septoclasts (SCs), which express both fatty acid-binding protein 5 and platelet-derived growth factor beta, are mononuclear cartilage-resorbing cells predominantly located at the chondro-osseous junction of the growth plate (GP). These cells originate from pericytes (PCs). Cathepsin B (CTSB) and matrix metalloproteinase-13 (MMP13), expressed in SCs, participate in the degradation of collagen and other cartilage matrices. This study aimed to investigate the involvement of the ETS proto-oncogene 1 (ETS1) in the transcription of Ctsb and Mmp13 during the differentiation of SCs from PCs. ETS1 was localized in SCs and a small number of PCs during development and postnatal stages. Upregulation of Ets1, Mmp13, Ctsb, and the Ets1-related genes, specificity protein 1 (Sp-1), jun proto-oncogene (c-Jun), and cAMP response element-binding protein-binding protein (Crebbp) in SCs compared with those in PCs was shown by RNA-seq analysis of samples isolated from the tibiae of 3-week-old postnatal mice. The Ets1-related proteins were localized ubiquitously in SCs and PCs in the GP. In primary SC cultures, the expression levels of Ctsb and Mmp13 were significantly reduced following treatment with Ets1 siRNA. Thus, our results revealed that ETS1 promoted the expression of Ctsb and Mmp13 in SCs during the differentiation of SCs from PCs.