Deficiency of EXT1 and FGFR3 genes promotes chondrocyte differentiation, leading to the induction of osteochondroma formation.

Objective: This study aims to investigate the roles of the EXT1 and FGFR3 genes in the development of osteochondromas, focusing specifically on their potential interactions in chondrocyte proliferation, differentiation, and tumor formation.

Methods: In vitro, the ATDC5 chondroprogenitor cell line was used to examine the effects of inactivation of both EXT1 and FGFR3. In vivo, a mouse model with dual gene knockout of Ext1 and Fgfr3 was constructed to further explore these genes' roles in tumor formation by observing the incidence and distribution patterns of osteochondromas.

Results: The in vitro experiments demonstrated that ATDC5 cells with reduced expression of EXT1 and FGFR3 genes exhibited enhanced chondrogenic differentiation. In vivo, Fgfr3^+/-;Ext1^+/- mice showed a significant incidence of osteochondromas (72.7 %), primarily located in the humerus, fibula, and tibia, while mice with a single heterozygous deletion did not display notable lesions.

Conclusion: The EXT1 and FGFR3 genes play crucial regulatory roles in the development of osteochondromas. Deficiencies in Ext1 and Fgfr3 can induce the formation of osteochondromas.