International Journal of Endocrinology

Review Article

Functional Diversity of Fibroblast Growth Factors in Bone Formation

Table 1

Roles of FGFs in bone.


FGFs		Models				Outcomes	Animals	Ref.
		In vivo		Ex vivo	In vitro
Types	Members	Genetic manipulations	Recombinant proteins	Ex vivo	Recombinant proteins and so forth

Canonical	FGF1	Systemic deletion				No obvious effects	Mice	[31]
			Injections over the calvaria			Osteoblastic cell proliferation and new bone formation ↑	Mice	[24]
			Intravenous injections			Prevention of the ovariectomized (OVX)-related bone loss	OVX Rats	[24]
					Osteoblasts	Cell proliferation ↑, but nodule formation and mineralization ↓	Rats	[30]
	FGF2	Systemic deletion		Calvaria cells		Cell proliferation ↓	Mice	[26]
				Bone marrow cells		ALP-positive colonies and mineralized nodules ↓	Mice	[26, 28]
						Trabecular bone ↓	Mice	[26, 28]
		Osteoblast-specific expression of human HMW FGF2				Dwarfism, osteomalacia, none mineral density ↓, serum phosphate levels, and FGF23 expression ↑	Mice	[95]
		Osteoblast-specific expression of human HMW FGF2					Mice	[95]
		Osteoblast-specific expression of human LMW FGF2		Bone marrow cells		ALP-positive colonies and mineralized nodules ↑	Mice	[29]
		Osteoblast-specific expression of human LMW FGF2				Increased bone formation ↑, sFRP-1 expression ↓
		Systemic deletion of human LMW FGF2		Bone marrow cells		Reverse effects as above
		Systemic deletion of human LMW FGF2				Reverse effects as above
			Intravenous injections			Growth plate width and trabecular bone ↑ and periosteal bone ↓	Rats	[23]
			Subcutaneously injections			Osteoid volume in lumbar vertebra ↑	OVX Rats	[25]
			Injections over the calvaria			Osteoblastic cell proliferation and new bone formation ↑	Mice	[24]
			Single local injection into the distracted callus			Bone formation in the callotasis model ↑	Rabbits	[21]
			Subcutaneous transplantations of human bone marrow cells treated with FGF2			New bone formation in trabecular bone ↑	Nude mice	[37]
					Bone marrow cells	Cell proliferation and matrix mineralization ↑	Humans	[37]
					Calvaria cells	Cell proliferation ↑, matrix mineralization ↓	Mice	[39]
						Differentiation stage-specific effects; cell proliferation ↑,	Humans	[20]
						Osteogenic differentiation ↓ in less mature cells
						Matrix mineralization ↑ in more mature cells
					Osteoblasts from trabecular bone	Cell proliferation ↑, ALP activity, and matrix mineralization ↓	Humans	[33]
	FGF4		Subcutaneous injections			Bone formation ↑	Mice	[32]
	FGF6				Osteoblasts from trabecular bone	Cell proliferation ↑, ALP activity, and matrix mineralization ↓	Humans	[33]
	FGF7				Embryonic stem cells	Mineralized nodules and osteoblast marker gene expression ↑	Mice	[34]
	FGF8				Osteogenic ROB-26 cells	ALP activity and Runx2 expression ↑	Rats	[35]
	FGF9		Subcutaneous transplantations of human bone marrow cells treated with FGF2 plus FGF9			Effect of FGF2 on new bone formation in trabecular bone ↑	Nude mice	[37]
	FGF9				Bone marrow cells	Effect of FGF2 on cell proliferation and mineralization ↑	Humans	[37]
	FGF10	Systemic deletion in Fgfr2 mutant mice				Rescue of craniosynostosis and skeletal defects	Mice	[38]
	FGF10				Calvaria cells	No obvious effects	Mice	[39]
	FGF18	Systemic deletion				Skeletal defects, proliferation of osteogenic cells, and maturation of osteoblasts ↓	Mice	[40]
	FGF18				Calvaria cells	Cell proliferation ↑, matrix mineralization ↓	Mice	[39]

Hormone-like	FGF21	Overexpression				Trabecular bone ↓	Mice	[92]
	FGF21	Systemic deletion				Reverse effects as above	Mice	[92]
	FGF23	Systemic deletion				Bone mineralization ↓ with hyperphosphatemia	Mice	[81]
		Overexpression				Bone abnormality with hypophosphatemia and serum PTH levels ↑	Mice	[57]
		Osteoblast-specific overexpression of FGF23					Mice	[58]
					Calvaria cells with adenoviral FGF23 overexpression	Osteogenic differentiation and matrix mineralization ↓	Rats	[9]
					Osteoblastic MC3T-E1 cells	Cell proliferation ↑, matrix mineralization ↓	Mice	[87]

↑: increase; ↓: decrease. Ref.: References.