Fam20b-catalyzed Glycosylation Regulates the Chondrogenic and Osteogenic Differentiation of Embryonic Condyle

Although the roles of proteoglycans (PGs) have been well documented in the development and homeostasis of temporomandibular joint (TMJ), how the glycosaminoglycan (GAG) chains of PGs fulfill the roles still requires explication. In this study, we found that inactivation of Fam20b in craniofacial neural crest cells (CNCCs) dramatically reduced the synthesis and accumulation of GAG chains, rather than the core proteins in condylar cartilage, which resulted in a hypoplastic condylar cartilage by severely promoting chondrocyte hypertrophy and bone collar ossification. To identify the gene transcriptomic alteration by Fam20b inactivation, bulk RNA-sequencing of WT and Wnt1-cre;Fam20bf/f condyle at E16.5 was conducted. We first analyzed RNA-Seq data to assess the expression level of Fam20b and key components in Ihh, Wnt, BMP and FGF singalings. And then, further analysis revealed that differential expressed genes (DEGs) were mainly enriched in bone- and ECM- related biological processes, especially in bone development. Overall, we used bulk RNA Seq and molecular experiments to reveal a comprehensive role of the Fam20b-catalyzed GAG chain synthesis in the chondrogenic and osteogenic differentiation of the developing TMJ condyle.