Effect and mechanism of recombinant human fibroblast growth factor 18 on osteoporosis in OVX mice

This study aimed to investigate the effect and the mechanism of recombinant human fibroblast growth factor 18 (rhFGF18) on postmenopausal osteoporosis.

The effect of rhFGF18 on the proliferation and apoptosis of osteoblasts and the mechanism underlying such an effect was evaluated using an oxidative stress model of the MC3T3-E1 cell line. Furthermore, ovariectomy was performed on ICR mice to imitate estrogen-deficiency postmenopausal osteoporosis. Bone metabolism and bone morphological parameters in the ovariectomized (OVX) mice were evaluated.

The results obtained from the cell model showed that FGF18 promoted MC3T3-E1 cell proliferation by activating the extracellular signal-regulated kinase (ERK) and p38 instead of c-Jun N-terminal kinase (JNK). FGF18 also prevented cells from damage inflicted by oxidative stress via inhibition of apoptosis. After FGF18 administration, the expression level of anti-apoptotic protein Bcl-2 in the mice was upregulated, whereas those of the pro-apoptotic proteins Bax and caspase-3 were downregulated. Administering FGF18 also improved bone metabolism and bone morphological parameters in OVX mice.

FGF18 could effectively prevent bone loss in OVX mice by enhancing osteoblastogenesis and protecting osteoblasts from oxidative stress-induced apoptosis.