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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (7): 66-73.doi: 10.6040/j.issn.1671-7554.0.2022.0183

• 基础医学 • 上一篇    下一篇

Sdccag3通过Wnt通路对高脂血症大鼠种植体骨结合的影响

袁孟绮,霍凤蕾,任会萍,郭秋爽,蓝菁   

  1. 山东大学齐鲁医学院口腔医学院·口腔医院修复科 山东省口腔组织再生重点实验室 山东省口腔生物材料与组织再生工程实验室, 山东 济南 250012
  • 发布日期:2022-07-27
  • 通讯作者: 蓝菁. E-mail:lanjing@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(82170999)

Effects of Sdccag3 on the osseointegration in hyperlipidemia rats through Wnt pathway

YUAN Mengqi, HUO Fenglei, REN Huiping, GUO Qiushuang, LAN Jing   

  1. Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &
    Shandong Key Laboratory of Oral Tissue Regeneration &
    Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, Shandong, China
  • Published:2022-07-27

摘要: 目的 探讨Sdccag3在高脂环境中通过Wnt信号通路影响骨髓间充质干细胞(BMSCs)成脂成骨分化以及高脂血症大鼠种植体周围骨结合的能力。 方法 构建高脂血症大鼠模型以及高脂环境培养BMSCs并进行成骨诱导,慢病毒载体过表达/沉默结肠癌抗原3(Sdccag3)的表达,采用RT-PCR、Western blotting、Micro-CT以及硬组织切片HE染色、油红O染色、免疫荧光染色等方法检测高脂环境中Sdccag3对大鼠骨代谢以及BMSCs分化平衡的影响。 结果 高脂成骨诱导BMSCs后过表达Sdccag3,下调成脂分化指标脂肪酸结合蛋白4(FABP4)、过氧化物酶体增殖剂激活受体γ(PPAR-γ),并上调Wnt信号通路标志基因低密度脂蛋白受体相关蛋白 5(LRP5)、LRP6、β-catenin及Wnt5a、Wnt5b,上调成骨分化指标碱性磷酸酶(ALP)、 Runt相关的转录因子2(Runx2);在高脂血症大鼠种植体周围骨组织中,过表达Sdccag3可上调Wnt信号通路标志基因并抑制周围脂形成,沉默LRP5会下调Sdccag3、成骨分化指标,上调成脂分化指标,与沉默Sdccag3表达一致。 结论 高脂血症促进种植体周围脂肪形成并抑制Sdccag3表达;过表达Sdccag3抑制BMSCs成脂分化并降低高脂血症大鼠种植体周围的成脂,促进成骨,促进Wnt信号通路标志基因表达。

关键词: 高脂血症, Sdccag3, 成脂分化, Wnt通路, 低密度脂蛋白受体相关蛋白 5

Abstract: Objective To investigate the effects of serologically defined colon cancer antigen-3(Sdccag3)on the differentiation of bone marrow mesenchymal stem cells(BMSCs)and the osteointegration around implants in hyperlipidemia rats through Wnt signaling pathway in high lipid environment. Methods BMSCs were cultured in hyperlipidemia rat models and induced by high lipid environment. Sdccag3 expression was overexpressed/silenced by lentivirus vector. RT-PCR, Western blotting, Micro-CT, HE staining, Oil red O staining and immunofluorescence staining were used to assess the effects of high lipid environment and Sdccag3 on bone metabolism and BMSCs differentiation balance. Results Sdccag3 was overexpressed in BMSCs induced by high lipid osteogenesis, which inhibited lipid differentiation indexes peroxisome proliferators-activated receptors γ(FABP4)and peroxisome proliferators-activated receptors γ(PPAR-γ), up-regulated Wnt signaling pathway marker genes low density lipoprotein receptor-related protein 5(LRP5), low density lipoprotein receptor-related protein 6(LRP6), β-catenin, Wnt family member 5a(Wnt5a)and Wnt family member 5b(Wnt5b), and promoted osteogenic differentiation indexes alkaline phosphatase(ALP)and runt-related transcription factor 2(Runx2). In hyperlipidemia rats, overexpression of Sdccag3 up-regulated Wnt signaling pathway marker genes and inhibited peripheral lipid formation, while silencing LRP5 down-regulated Sdccag3, inhibited osteogenic differentiation and promoted lipid differentiation, which were consistent with silencing Sdccag3 expression. Conclusion Hyperlipidemia inhibits Sdccag3 expression. Overexpression of Sdccag3 inhibits adipogenic differentiation of BMSCs and decreases lipid formation around the implants in hyperlipidemia rats, promotes osteogenesis and expression of Wnt signaling pathway marker genes.

Key words: Hyperlipidemia, Sdccag3, Adipogenesis, Wnt pathway, Low density lipoprotein receptor-related protein 5

中图分类号: 

  • R783
[1] Kuropka P, Zwyrzykowska-Wodzińska A, Kupczyński R, et al. The Effect of Ilex × meserveae S. Y. Hu Extract and Its Fractions on Renal Morphology in Rats Fed with Normal and High-Cholesterol Diet [J]. Food, 2021, 10(4): 818.
[2] Szekanecz Z, Raterman HG, Pethö Z, et al. Common mechanisms and holistic care in atherosclerosis and osteoporosis [J]. Arthritis Res Ther, 2019, 21(1): 15.
[3] Gaudio A, Xourafa A, Rapisarda R, et al. Peripheral artery disease and osteoporosis: Not only age-related(Review)[J]. Mol Med Rep, 2018, 18(6): 4787-4792.
[4] Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers [J]. J Cachexia Sarcopenia Muscle, 2020, 11(3): 609-618.
[5] Parveen B, Parveen A, Vohora D. Biomarkers of osteoporosis: an update [J]. Endocr Metab Immune Disord Drug Targets, 2019, 19(7): 895-912.
[6] Daubert DM, Weinstein BF, Bordin S, et al. Prevalence and predictive factors for peri-implant disease and implant failure: a cross-sectional analysis [J]. J Periodontol, 2015, 86(3): 337-347.
[7] Wu S, Yu Q, Lai A, et al. Pulsed electromagnetic field induces Ca2+-dependent osteoblastogenesis in C3H10T1/2 mesenchymal cells through the Wnt-Ca2+/Wnt-β-catenin signaling pathway [J]. Biochem Biophys Res Commun, 2018, 503(2): 715-721.
[8] Ren HP, Wang ZF, Xu JZ, et al. The Impact of Frizzled-9 on Dental Implant Osseointegration in Hyperlipidemic Rats [J]. J Hard Tissue Biol, 2020, 29(1): 37-44.
[9] Pino AM, Rosen CJ, Rodríguez JP. In osteoporosis, differentiation of mesenchymal stem cells(MSCs)improves bone marrow adipogenesis [J]. Biol Res, 2012, 45(3): 279-287.
[10] Huang X, Wang Z, Li D, et al. Study of microRNAs targeted Dvl2 on the osteoblasts differentiation of rat BMSCs in hyperlipidemia environment [J]. J Cell Physiol, 2018, 233(9): 6758-6766.
[11] Chen X, Luo Y, Jia G, et al. FTO promotes adipogenesis through Inhibition of the Wnt/β-catenin signaling pathway in porcine intramuscular preadipocytes [J]. Anim Biotechnol, 2017, 28(4): 268-274.
[12] Ma EB, Sahar NE, Jeong M, et al. Irisin exerts inhibitory effect on adipogenesis through regulation of Wnt signaling [J]. Front Physiol, 2019, 10: 1085. doi:10.3389/fphys.2019.01085.
[13] Han L, Wang B, Wang R, et al. The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor [J]. Stem Cell Res Ther, 2019, 10(1): 377.
[14] Thim T, Scholz KJ, Hiller KA, et al. Radiographic bone loss and its relation to patient-specific risk factors, LDL cholesterol, and vitamin D: a cross-sectional study [J]. Nutrients, 2022, 14(4): 864.
[15] Di Murro B, Papi P, Letizia C, et al. The prevalence of peri-implant diseases in patients with metabolic syndrome: a case-control study on an Italian population sample [J]. Minerva Stomatol, 2019, 68(4): 143-149.
[16] Kwon M, Rubio G, Nolan N, et al. FILIP1L loss is a driver of aggressive mucinous colorectal adenocarcinoma and mediates cytokinesis defects through PFDN1[J]. Cancer Res, 2021, 81(21): 5523-5539.
[17] Kvainickas A, Orgaz AJ, Nägele H, et al. Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50 [J]. J Cell Sci, 2017, 130(2): 382-395.
[18] Cui Y, Yang Z, Flores-Rodriguez N, et al. Formation of retromer transport carriers is disrupted by the Parkinson disease-linked Vps35 D620N variant [J]. Traffic, 2021, 22(4): 123-136.
[19] Hu J, Harris PC. Regulation of polycystin expression, maturation and trafficking [J]. Cell Signal, 2020, 72: 109630. doi:10.1016/j.cellsig.2020.109630.
[20] Hua Y, Yang Y, Li Q, et al. Oligomerization of frizzled and LRP5/6 protein initiates intracellular signaling for the canonical WNT/β-catenin pathway [J]. J Biol Chem, 2018, 293(51): 19710-19724.
[21] d'Angelo M, Castelli V, Catanesi M, et al. PPARγ and cognitive performance [J]. Int J Mol Sci, 2019, 20(20): 5068.
[22] Martínez-Gil N, Ugartondo N, Grinberg D, et al. Wnt pathway extracellular components and their essential roles in bone homeostasis [J]. Genes(Basel), 2022, 13(1): 138.
[23] Chen T, Gao F, Luo D, et al. Cistanoside a promotes osteogenesis of primary osteoblasts by alleviating apoptosis and activating autophagy through involvement of the Wnt/β-catenin signal pathway [J]. Ann Transl Med, 2022, 10(2): 64.
[24] Ju S, Lim L, Wi K, et al. LRP5 regulates HIF-1α stability via interaction with PHD2 in ischemic myocardium [J]. Int J Mol Sci, 2021, 22(12): 6581.
[25] Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities[J]. Cell, 2017, 169(6):985-999.
[26] Sebastian A, Hum NR, Murugesh DK, et al. Wnt co-receptors Lrp5 and Lrp6 differentially mediate Wnt3a signaling in osteoblasts [J]. PLoS One, 2017, 12(11): e0188264. doi: 10.1371/journal.pone.0188264.
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