Chsy1 deficiency reduces extracellular matrix productions and aggravates cartilage injury in osteoarthritis

•Osteoarthritis (OA) is one of the most common chronic bone and joint diseases in the world. More than 528 million people are affected by OA worldwide. At present, there is no effective clinical treatment for OA except analgesic and joint replacement.•CHSY1, as one of six glycosyltransferases, was found to be decreased in the knee chondrocytes of OA rats. In this study, we were trying to explore the role of CHSY1 in chondrogenesis and OA. We found: (1) Chsy1 deficiency resulted in the reduction of extracellular matrix production in chondrocyte and the promotion of endochondral osteogenesis, which were considered to be the characteristics of osteoarthritis; (2) in differentiated chondrocytes cells, knockdown of Chsy1 could upregulate BMP signaling; (3) the reduction of the extracellular matrix productions and promotion of endochondral osteogenesis could be rescued by BMP signaling inhibitor LDN193189 or by Chsy1 overexpression. These studies implicated that Chsy1 might regulate the extracellular matrix productions and endochondral osteogenesis through BMP signaling, and the lack of Chsy1 could aggravate the cartilage damage of osteoarthritis.•Here, we proposed the important role of CHSY1 in chondrocyte differentiation and endochondral ossification, which might contribute to the in-depth study on the pathogenesis of human osteoarthritis. Osteoarthritis (OA) is a kind of degenerative joint disease marked by the destruction of articular cartilage due to the degeneration of chondrocytes. CHSY1, one of the glycosyltransferases, is involved in the synthesis of chondroitin sulfate. Herein, we found that the expression of Chsy1 was decreased in the knee cartilage of OA rats. In order to investigate the role of CHSY1 in chondrogenesis and OA, we established a Chsy1 stable knockdown cell line in mouse ATDC5 chondrocytes by lentivirus. It was found that Chsy1 deficiency resulted in a reduction of extracellular matrix production in chondrocytes and a promotion of endochondral osteogenesis, which was indicated by the decreased expression of early chondrocytes genes (Col2a1, Sox9), and the increased expression of cartilage hypertrophy genes (Col10a1, Runx2, Mmp13, Mmp3). The expression trend of these genes is considered to be the characteristic of osteoarthritis. In addition, knockdown of Chsy1 could upregulate BMP signaling in differentiated chondrocytes, whereas Chsy1 overexpression had opposite effects. The reduction of extracellular matrix production and the promotio