Recombinant human FGF-18 protein

Summary

• High purity human protein (Uniprot number: O76093)
• 20.2 kDa (monomer)
• >98%, by SDS-PAGE quantitative densitometry
• Expressed in E. coli
• Animal origin-free (AOF) and carrier protein-free
• Manufactured in Qkine's Cambridge, UK laboratories
• Lyophilized from Tris, NaCl
• Resuspend in sterile-filtered water at >50 µg/ml, add carrier protein if desired, prepare single use aliquots and store frozen at -20 °C (short-term) or -80 °C (long-term).

Featured applications

• Growth and proliferation of chondrocytes, fibroblasts and primary cells
• Expansion of induced pluripotent, embryonic and mesenchymal stem cells
• Directed chondrogenic differentiation of mesenchymal stem cells
• Directed osteogenic differentiation of mesenchymal stem cells
• Stimulation of angiogenesis and vascular network development
• Induction of cell migration, proliferation and extracellular matrix production

Bioactivity

Purity

Qkine FGF-18 is as biologically active as a comparable alternative supplier protein. Quantitative luciferase reporter assay shows equivalent bioactivity of Qkine FGF-18 (Qk069, green) and alternative supplier FGF-18 (Supplier B, black). HEK293T reporter cells were treated in triplicate with a serial dilution of FGF-18 for 3 hours. Firefly luciferase activity is measured and normalized to control Renilla luciferase activity.

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.

Background references

1. Ornitz, D. M. and Itoh, N. Fibroblast growth factors. Genome Biol 2, reviews3005.1 (2001). doi: 10.1186/gb-2001-2-3-reviews3005
2. Ohbayashi, N. et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 16, 870–879 (2002). doi: 10.1101/gad.965702
3. Liu, Z., Xu, J., Colvin, J. S. and Ornitz, D. M. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev. 16, 859–869 (2002). doi: 10.1101/gad.965602
4. Davidson, D. et al. Fibroblast Growth Factor (FGF) 18 Signals through FGF Receptor 3 to Promote Chondrogenesis. Journal of Biological Chemistry 280, 20509–20515 (2005). doi: 10.1074/jbc.M410148200
5. Tomanek, R. J. et al. Embryonic coronary vasculogenesis and angiogenesis are regulated by interactions between multiple FGFs and VEGF and are influenced by mesenchymal stem cells. Developmental Dynamics 239, 3182–3191 (2010). doi: 10.1002/dvdy.22460
6. Ornitz, D. M. and Itoh, N. The Fibroblast Growth Factor signaling pathway. WIREs Developmental Biology 4, 215–266 (2015). doi: 10.1002/wdev.176
7. Shu, C., Smith, S. M., Little, C. B. and Melrose, J. Use of FGF-2 and FGF-18 to direct bone marrow stromal stem cells to chondrogenic and osteogenic lineages. Future Science OA 2, FSO142 (2016). doi: 10.4155/fsoa-2016-0034
8. Huang, L. et al. Synergistic Effects of FGF-18 and TGF- β 3 on the Chondrogenesis of Human Adipose-Derived Mesenchymal Stem Cells in the Pellet Culture. Stem Cells International 2018, 1–10 (2018). doi: 10.1155/2018/7139485
9. Zhang, W., Ouyang, H., Dass, C. R. and Xu, J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4, 15040 (2016). doi: 10.1038/boneres.2015.40
10. Liu, Z., Lavine, K. J., Hung, I. H. and Ornitz, D. M. FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate. Developmental Biology 302, 80–91 (2007). doi: 10.1016/j.ydbio.2006.08.071
11. Belgacemi, R. et al. Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts. Front. Cell Dev. Biol. 11, 1220002 (2023). doi: 10.3389/fcell.2023.1220002
12. Zhang, J. et al. FGF18–FGFR2 signaling triggers the activation of c-Jun–YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential. Oncogene 39, 6647–6663 (2020). https://www.nature.com/articles/s41388-020-01458-x
13. Yao, X. et al. Fibroblast growth factor 18 exerts anti-osteoarthritic effects through PI3K-AKT signaling and mitochondrial fusion and fission. Pharmacological Research 139, 314–324 (2019). doi: 10.1016/j.phrs.2018.09.026
14. Danopoulos, S. et al. FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells. American Journal of Physiology-Lung Cellular and Molecular Physiology 324, L433–L444 (2023). doi: 10.1152/ajplung.00316.2022
15. Tsuchiya, Y. et al. Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis. Nat Commun 14, 6304 (2023). doi: 10.1038/s41467-023-42058-z
16. Chen, X. et al. Integration Capacity of Human Induced Pluripotent Stem Cell-Derived Cartilage. Tissue Engineering Part A 25, 437–445 (2019). doi: 10.1089/ten.TEA.2018.0133