FGF1 couples collagen secretion and trafficking to drive osteogenic differentiation.

The osteoblast differentiation is essential for skeletal development and homeostasis, and its dysregulation leads to severe bone defects and impaired skeletal integrity. Identifying key regulators of this process is therefore crucial for advancing regenerative medicine in orthopedics. FGF1 (Fibroblast growth factor 1) is highly expressed in neural crest-derived osteoprogenitors, its function in osteoblast differentiation remains unclear. Here, we demonstrate that FGF1 is a critical regulator of osteogenesis. In MC3T3-E1 preosteoblasts, FGF1 knockdown significantly impaired cell proliferation and osteogenic differentiation, as evidenced by reduced ALP activity and downregulation of Runx2, SP7, and COL1A1, all of which are reversible upon FGF1 supplementation. Importantly, we found that FGF1 loss disrupts intracellular trafficking and secretion of type I collagen, suggesting that FGF1 promotes osteogenic differentiation and matrix mineralization, at least in part, by facilitating collagen synthesis and secretion. However, whether type I collagen is the key mediator of FGF1's pro-osteogenic effects warrant further investigation. Nonetheless, this study identifies FGF1-related pathways as potential therapeutic targets for bone disorders.