|
|
Promotion of GDF11 on osteoblast differentiation of ADSCs derived from diabetic mice by activating PI3K/Akt signaling pathway |
GONG Min1, ZHU Biao2, LI Xin3, MEI Mei1, DANG Ruijie2, CHEN Ye1 |
1. Department of Stomatology, Yuquan Hospital of Tsinghua University, Beijing 100040, China; 2. PLA Medical School, Beijing 100853, China; 3. Department of Stomatology, Beijing Shijingshan Hospital, Beijing 100043, China |
|
|
Abstract Objective To investigate the effects of growth differentiation factor 11 (GDF11) on osteoblast differentiation of adipose derived stem cells (ADSCs) from diabetic mice and related signaling mechanism. Methods ADSCs from diabetic mice were isolated and cultured. The effect of GDF11 on the proliferation of ADSCs was detected by flow cytometry. After cultured in osteogenic differentiation medium, ALP activity was detected, qPCR was used to evaluate the expression of osteoblast genes, and phosphorylation levels of PI3K and Akt were detected by western blot. Results Cell proliferation was less affected by GDF11 intervation, promoted ALP activity in a concentration-dependent but saturated manner, significantly upregulated mRNA expression of Runx2 (2.41±0.19) vs. (1.00±0.11)], Osx [(1.41±0.21) vs. (1.00±0.10)] and ALP [(1.42±0.20) vs. (1.00±0.09)] (P<0.05), and significantly increased phosphorylation levels of PI3K [(2.84±0.19) vs. (1.00±0.11)] and Akt [(4.58±0.20) vs. (1.00±0.19)] (P<0.05). Moreover, the effects of GDF11 on promoting osteoblast differentiation of ADSCs from diabetic mice was partially weakened by the PI3K inhibitor LY294002. Conclusions GDF11 promotes osteoblast differentiation of ADSCs from diabetic mice, and its mechanism may be related with the activation of PI3K/Akt signaling pathway.
|
Received: 05 May 2023
|
|
|
|
|
[1] |
Danaei G, Finucane M M, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants[J]. Lancet, 2011,378(9785):31-40.
|
[2] |
孙丽娜,修双玲,王 立,等. 老年2型糖尿病合并代谢综合征患者认知障碍的危险因素分析[J]. 中国医药, 2020, 15(3):393-396.
|
[3] |
孙 龙,薛鹏飞,侯小青,等. BMP-7对高糖环境下成骨细胞生物学性能的影响[J]. 实用口腔医学杂志, 2017, 33 (6):735-739.
|
[4] |
Gao J, Wang H, Shen J, et al. Mutual regulation between GDF11 and TET2 prevents senescence of mesenchymal stem cells[J]. J Cell Physiol, 2023.
|
[5] |
Mei W, Xiang G, Li Y, et al. GDF11 protects against endothelial injury and reduces atherosclerotic lesion formation in apolipoprotein E-null mice[J]. Mol Ther, 2016,24(11):1926-1938.
|
[6] |
Li H, Li Y, Xiang L, et al. GDF11 attenuates development of type 2 Diabetes via improvement of islet β-cell function and survival[J]. Diabetes, 2017,66(7):1914-1927.
|
[7] |
Zhang J, Li Y, Li H, et al. GDF11 improves angiogenic function of EPCs in diabetic limb ischemia[J]. Diabetes, 2018,67(10):2084-2095.
|
[8] |
刘 翠,徐晓丽,李金儒,等. 髓源性生长因子对糖尿病小鼠BMSCs骨向分化的影响及机制研究[J]. 实用口腔医学杂志, 2020,36(6):865-869.
|
[9] |
杨文朋,马雨聪,张佳佳,等. 神经调节蛋白1对2型糖尿病小鼠骨髓间充质干细胞成骨分化的影响[J]. 北京口腔医学, 2022,30(2):107-110.
|
[10] |
朱丽利,杨德圣,朱 彪,等. 利拉鲁肽促进犬骨髓间充质干细胞骨向分化的体外研究[J]. 口腔颌面修复学杂志, 2018,19(1):44-47.
|
[11] |
Loffredo F S, Steinhauser M L, Jay S M, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy[J]. Cell, 2013,153(4):828-839.
|
[12] |
Katsimpardi L, Litterman N K, Schein P A, et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors[J]. Science, 2014,344(6184):630-634.
|
[13] |
Sinha M, Jang Y C, Oh J, et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle[J]. Science, 2014,344(6184):649-652.
|
[14] |
Zhang C, Lin Y, Liu Q, et al. Growth differentiation factor 11 promotes differentiation of MSCs into endothelial-like cells for angiogenesis[J]. J Cell Mol Med, 2020,24(15):8703-8717.
|
[15] |
Zhao Y, Zhu J, Zhang N, et al. GDF11 enhances therapeutic efficacy of mesenchymal stem cells for myocardial infarction via YME1L-mediated OPA1 processing[J]. Stem Cells Transl Med, 2020,9(10):1257-1271.
|
[16] |
Zhang Y, Shao J, Wang Z, et al. Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma[J]. Gene, 2015,557(2):209-214.
|
[17] |
Shen G S, Zhou H B, Zhang H, et al. The GDF11-FTO-PPARγ axis controls the shift of osteoporotic MSC fate to adipocyte and inhibits bone formation during osteoporosis[J]. Biochim Biophys Acta Mol Basis Dis, 2018,1864(12):3644-3654.
|
[18] |
Lu Q, Tu M L, Li C J, et al. GDF11 inhibits bone formation by activating Smad2/3 in bone marrow mesenchymal stem cells[J]. Calcif Tissue Int, 2016,99(5):500-509.
|
[19] |
Liu W, Zhou L, Zhou C, et al. GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation[J]. Nat Commun, 2016,7:12794.
|
[20] |
Wang S, Wang L, Shi S, et al. Inhibition of GDF11 could promote bone healing in the tooth extraction socket and facilitate mesenchymal stem cell osteogenic differentiation in T2DM pigs[J]. J Periodontol, 2020,91(12):1645-1652.
|
[21] |
张志华,徐娟娟,闫胜男,等. GDF11通过介导PI3K/AKT通路对人牙髓干细胞体外矿化能力的影响研究[J]. 实用口腔医学杂志, 2023,39(2):223-227.
|
[22] |
Meng J, Ma X, Wang N, et al. Activation of GLP-1 receptor promotes bone marrow stromal cell osteogenic differentiation through β-catenin[J]. Stem Cell Reports, 2016,6(4):579-591.
|
[23] |
张 璇,王 辰,杨 琳,等. 炎症微环境下过表达Wnt5a对人牙周膜干细胞增殖和成骨分化的影响[J]. 解放军医学院学报,2023:1-9.
|
[24] |
翟 羽,焦 婷,郭红延,等. GDF11抑制小鼠BMSCs成骨分化的机制研究[J]. 临床口腔医学杂志, 2020, 36(4):195-198.
|
[25] |
Ding Y, Jiang H, Meng B, et al. Sweroside-mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation[J]. J Cell Biochem, 2019,120(9):16025-16036.
|
|
|
|