Recombinant human FGF-18 protein (Qk069)

Protein background

Fibroblast Growth Factor 18 (FGF-18), a member of the fibroblast growth factor (FGF) family is characterized by its heparin-binding properties and involved in diverse biological processes such as embryonic development, tissue repair, and cellular regulation [1]. FGF-18 is normally expressed in adult tissues undergoing regeneration and plays crucial roles in skeletal development and repair [2], highlighting its importance in tissue homeostasis and repair mechanisms.

Specifically, FGF-18 exerts significant effects on skeletal biology by regulating endochondral bone formation, chondrocyte proliferation and differentiation, and osteogenesis [3]. It also contributes to cartilage maintenance by promoting articular chondrocyte proliferation and integrity in joints [4]. Additionally, FGF-18 participates in angiogenesis, promoting new blood vessel formation during tissue repair [5], and has demonstrated benefits in wound healing by enhancing cell proliferation, migration, and extracellular matrix production [4].

Beyond its roles in skeletal development, cartilage maintenance and tissue repair, FGF18 has significant implications in cell culture systems. FGF-18 is a potent mitogen that stimulates cell proliferation and activates intracellular signaling pathways like MAPK and PI3K-Akt, crucial for cell growth and survival [6]. FGF-18 serves as a supplement in growth media to support primary cell expansion, including chondrocytes and fibroblasts while also maintaining and directing the differentiation of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) [7-9,16]. Combined with other growth factors, FGF-18 helps sustain the undifferentiated state of stem cells and prevents spontaneous differentiation.

Furthermore, FGF-18 plays a pivotal role in regulating chondrogenesis and osteogenesis, enhancing the differentiation of mesenchymal progenitor cells into chondrocytes and osteoblasts, crucial for cartilage and bone formation [3,7-8]. Recent studies have also highlighted the role of FGF-18 in other processes such as a role in lung organogenesis by promoting lunch branching morphogenesis using mesenchymal progenitor cells [14], induction of liver fibrosis through hepatic stellate cells [15]. Its angiogenic properties facilitate endothelial cell proliferation and migration, aiding in the development of functional vascular networks in tissue engineering applications [4].

Structurally, FGF-18 shares common features with other FGFs, consisting of a core domain responsible for binding to FGF receptors (FGFRs), particularly FGFR1c, FGFR2c, FGFR3c and FGFR4 and heparan sulfate proteoglycans (HSPGs), essential for ligand-receptor interaction and subsequent signal transduction. Upon binding to specific FGFRs like FGFR3 and FGFR4, FGF-18 triggers receptor dimerization and activates downstream signaling pathways, notably Ras-MAPK and PI3K-Akt, regulating diverse biological processes [3, 10-13].

Due to its roles in tissue repair and regeneration, FGF-18 is being explored as a potential therapeutic agent for musculoskeletal disorders such as osteoarthritis, osteoporosis, and bone fractures [9]. Early studies and trials have investigated FGF-18-based therapies to promote cartilage repair and bone regeneration, underscoring its therapeutic potential pending further research into efficacy and safety in clinical settings [9].

In summary, FGF-18 is a multifunctional growth factor pivotal in skeletal development, cartilage maintenance, angiogenesis, and tissue repair. Its diverse biological functions make it a promising candidate for therapeutic interventions targeting tissue regeneration and treatment of musculoskeletal disorders.