Molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia.

The FGFR3 gene encodes fibroblast growth factor receptor 3 protein, a negative regulator of chondrogenesis. Gain-of-function mutations result in constitutively activated FGFR3, leading to aberrant signal transduction, and accounting for inhibition of chondrocyte proliferation and differentiation. Generally, these pathogenic mutations maintain FGFR3 in an active state and cause diverse phenotypes in patients with skeletal dysplasia. For decades, studies have revealed the molecular mechanisms of constitutively activated FGFR3 and relevant therapeutic strategies. By modulating the FGFR3-induced signalling pathway with methods such as blocking binding between ligands and receptors, blocking tyrosine kinase activities, or antagonising the FGFR3 downstream signalling pathway, these strategies offer the possibility to ameliorate FGFR3 gene-related skeletal dysplasia phenotypes. In this review, we describe the mechanisms of potential therapeutic targets and underlying regulators and then systematically review molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia based on current knowledge.