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

IF 2.9 4区 医学 Q1 OBSTETRICS & GYNECOLOGY
Climacteric Pub Date : 2024-06-01 Epub Date: 2024-01-26 DOI:10.1080/13697137.2024.2302967
P Y Lu, M Huang, M H Shao, J X Hu, C Y Ding, Y J Feng, M Zhang, H P Lin, H S Tian
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Abstract

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

Methods: 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.

Results: 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.

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

重组人成纤维细胞生长因子 18 对 OVX 小鼠骨质疏松症的影响和机制
研究目的本研究旨在探讨重组人成纤维细胞生长因子18(rhFGF18)对绝经后骨质疏松症的影响及其机制:方法:使用 MC3T3-E1 细胞系的氧化应激模型评估 rhFGF18 对成骨细胞增殖和凋亡的影响及其作用机制。此外,还对 ICR 小鼠进行了卵巢切除,以模仿雌激素缺乏性绝经后骨质疏松症。对卵巢切除(OVX)小鼠的骨代谢和骨形态学参数进行了评估:细胞模型结果显示,FGF18 通过激活细胞外信号调节激酶(ERK)和 p38,而不是 c-Jun N 端激酶(JNK),促进 MC3T3-E1 细胞增殖。FGF18 还能通过抑制细胞凋亡防止细胞受到氧化应激的损伤。服用 FGF18 后,小鼠体内抗凋亡蛋白 Bcl-2 的表达水平上调,而促凋亡蛋白 Bax 和 caspase-3 的表达水平下调。服用 FGF18 还能改善 OVX 小鼠的骨代谢和骨形态学参数:结论:FGF18 可通过促进成骨细胞生成和保护成骨细胞免受氧化应激诱导的凋亡,有效防止 OVX 小鼠骨质流失。
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来源期刊
Climacteric
Climacteric 医学-妇产科学
CiteScore
1.70
自引率
7.10%
发文量
53
审稿时长
1 months
期刊介绍: Climacteric is the official journal of the International Menopause Society (IMS). As an international peer-reviewed journal it publishes original research and reviews of all aspects of aging in women. Climacteric was founded by the IMS in 1998 and today has become a leading journal in the publication of peer-reviewed papers on the menopause, climacteric and mid-life health. Topics covered include endocrine changes, symptoms attributed to the menopause and their treatment, hormone replacement and alternative therapies, lifestyles, and the counselling and education of peri- and postmenopausal women. Climacteric, published bimonthly, also features regular invited reviews, editorials and commentaries on recent developments. The editorial review board of Climacteric includes leading scientific and clinical experts in the field of midlife medicine and research and is headed by its Editor-in-Chief, Professor Rod Baber of Australia. He and his team of Associate Editors act independently to set a clear editorial policy, co-ordinate peer review, and ensure a rapid response to submitted papers.
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