Int J Stomatol ›› 2022, Vol. 49 ›› Issue (6): 641-647.doi: 10.7518/gjkq.2022103

• Original Articles • Previous Articles     Next Articles

Endothelial-cell-specific overexpression of Dickkopf 1 using Cadherin 5 promoter regulates osteogenesis in vivo

Yin Yijia1(),Yang Jinting1,Shen Jianqi2,Huang Lingyi1,Jing Yan3,Guan Qiuyue4(),Han Xianglong1   

  1. 1.State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
    2.Fenyang College of Shanxi Medical University, Lüliang 032299, China
    3.Baylor College of Dentistry, Texas A&M University, Dallas TX 75246, USA
    4.Geriatric Department, Caotang District, Sichuan Provincial People’s Hospital, Chengdu 610072, China
  • Received:2022-02-01 Revised:2022-07-15 Online:2022-11-01 Published:2022-11-03
  • Contact: Qiuyue Guan E-mail:yvonnist@163.com;qguan163@163.com
  • Supported by:
    Applied Basic Research Program of Science & Technology Department of Sichuan Province(2018JY0271)

Abstract:

Objective This study aimed to the expression of Dickkopf 1 (DKK1) during orthodontic tooth movement is examined. Then, the effects of endothelial-cell-specific overexpression of DKK1 on bone formation were detected. Moreover, the function of DKK1 on bone formation through endothelial cells was explained. Methods A rat orthodontic tooth movement model was constructed to detect the expression of DKK1 on the compressive and tensile side of alveolar bone. Then, R26-DKK1 and Cadherin 5 (Cdh5)-Cre mice were crossbred to produce transgenic mice expressing DKK1 in endothelial cells (Cdh5-Cre; R26-DKK1/R26-DKK1) and to detect the changes of bone morphology and bone volume of the femur and alveolar bone. Results During orthodontic tooth movement, DKK1 was highly expressed in the compressive side. DKK1 transgenic mice widely expressed DKK1 in the femur and alveolar bone, increased in bone density, narrowed in central bone marrow cavity, and increased in Trap+ cells numbers and collagen Ⅳ expression compared with wild type controls. Conclusion DKK1 might regulate orthodontic tooth movement. Endothelial-cell-specific overexpression of DKK1 using Cdh5 promoter is closely related to the differentiation of chondrocytes and the formation of trabecular bone, and causes increased expression level of collagen Ⅳ in periodontal tissue and bone.

Key words: endothelial cells, bone formation, femur, alveolar bone

CLC Number: 

  • R 782

TrendMD: 

Fig 1

Expression of DKK1 in femur and alveolar bone of DKK1 Tg mice"

Fig 2

Morphology and bone volume changes in DKK1 Tg mice"

Fig 3

Osteoclast activity in DKK1 Tg mice"

Fig 4

Expression of Col IV in DKK1 Tg mice"

1 Glinka A, Wu W, Delius H, et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction[J]. Nature, 1998, 391(6665): 357-362.
2 Jaschke N, Hofbauer LC, Göbel A, et al. Evolving functions of Dickkopf-1 in cancer and immunity[J]. Cancer Lett, 2020, 482: 1-7.
3 Zhang L, Tang Y, Zhu X, et al. Overexpression of MiR-335-5p promotes bone formation and regeneration in mice[J]. J Bone Miner Res, 2017, 32(12): 2466-2475.
4 Jang J, Jung Y, Kim Y, et al. LPS-induced inflammatory response is suppressed by Wnt inhibitors, Dickkopf-1 and LGK974[J]. Sci Rep, 2017, 7: 41612.
5 Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling[J]. Semin Arthritis Rheum, 2011, 41(2): 170-177.
6 Klavdianou K, Liossis SN, Sakkas L, et al. The role of Dickkopf-1 in joint remodeling and fibrosis: a link connecting spondyloarthropathies and scleroderma[J]. Semin Arthritis Rheum, 2017, 46(4): 430-438.
7 Ma Y, Zhang X, Wang M, et al. The serum level of Dickkopf-1 in patients with rheumatoid arthritis: a systematic review and meta-analysis[J]. Int Immunopharmacol, 2018, 59: 227-232.
8 Li J, Gong W, Li X, et al. Recent progress of wnt pathway inhibitor dickkopf-1 in liver cancer[J]. J Nanosci Nanotechnol, 2018, 18(8): 5192-5206.
9 Morvan F, Boulukos K, Clément-Lacroix P, et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass[J]. J Bone Miner Res, 2006, 21(6): 934-945.
10 Goes P, Dutra C, Lösser L, et al. Loss of dkk-1 in osteocytes mitigates alveolar bone loss in mice with periodontitis[J]. Front Immunol, 2019, 10: 2924.
11 Samiei M, Janjić K, Cvikl B, et al. The role of sclerostin and dickkopf-1 in oral tissues-a review from the perspective of the dental disciplines[J]. F1000Res, 2019, 8: 128.
12 Ribatti D, Nico B, Vacca A, et al. Endothelial cell heterogeneity and organ specificity[J]. J Hematother Stem Cell Res, 2002, 11(1): 81-90.
13 Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone[J]. Nature, 2014, 507(7492): 323-328.
14 Ke HZ, Richards WG, Li X, et al. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases[J]. Endocr Rev, 2012, 33(5): 747-783.
15 Klingenschmid G, Tschiderer L, Himmler G, et al. Associations of serum dickkopf-1 and sclerostin with cardiovascular events: results from the prospective Bruneck study[J]. J Am Heart Assoc, 2020, 9(6): e014816.
16 Yang L, Soonpaa MH, Adler ED, et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population[J]. Nature, 2008, 453(7194): 524-528.
17 Ueland T, Otterdal K, Lekva T, et al. Dickkopf-1 enhances inflammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2009, 29(8): 1228-1234.
18 Yamaguchi Y, Passeron T, Hoashi T, et al. Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes[J]. FASEB J, 2008, 22(4): 1009-1020.
19 Smadja DM, ’ Audigier C d, Weiswald LB, et al. The Wnt antagonist Dickkopf-1 increases endothelial progenitor cell angiogenic potential[J]. Arterioscler Thromb Vasc Biol, 2010, 30(12): 2544-2552.
20 Choi HJ, Park H, Lee HW, et al. The Wnt pathway and the roles for its antagonists, DKKS, in angiogenesis[J]. IUBMB Life, 2012, 64(9): 724-731.
21 Oh H, Ryu JH, Jeon J, et al. Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification[J]. J Bone Miner Res, 2012, 27(6): 1335-1344.
22 Baetta R, Banfi C. Dkk (Dickkopf) proteins[J]. Arterioscler Thromb Vasc Biol, 2019, 39(7): 1330-1342.
23 Ramli FF, Chin KY. A review of the potential application of osteocyte-related biomarkers, fibroblast growth factor-23, sclerostin, and dickkopf-1 in predicting osteoporosis and fractures[J]. Diagnostics (Basel), 2020, 10(3): E145.
24 Mäkitie RE, Kämpe A, Costantini A, et al. Biomarkers in WNT1 and PLS3 osteoporosis: altered concentrations of DKK1 and FGF23[J]. J Bone Miner Res, 2020, 35(5): 901-912.
25 Florio M, Gunasekaran K, Stolina M, et al. A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair[J]. Nat Commun, 2016, 7: 11505.
26 Rojas A, Mardones R, Pritzker K, et al. Dickkopf-1 reduces hypertrophic changes in human chondrocytes derived from bone marrow stem cells[J]. Gene, 2019, 687: 228-237.
27 Li W, Xiong Y, Chen W, et al. Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis[J]. Exp Ther Med, 2020, 20(3): 2631-2638.
28 Shimonishi M, Sato J, Takahashi N, et al. Expression of type Ⅳ collagen and laminin at the interface between epithelial cells and fibroblasts from human periodontal ligament[J]. Eur J Oral Sci, 2005, 113(1): 34-40.
29 Narimiya T, Wada S, Kanzaki H, et al. Orthodontic tensile strain induces angiogenesis via type Ⅳ collagen degradation by matrix metalloproteinase-12[J]. J Periodontal Res, 2017, 52(5): 842-852.
30 Foldager CB, Toh WS, Gomoll AH, et al. Distribution of basement membrane molecules, laminin and collagen type Ⅳ, in normal and degenerated cartilage tissues[J]. Cartilage, 2014, 5(2): 123-132.
31 Alva JA, Zovein AC, Monvoisin A, et al. VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells[J]. Dev Dyn, 2006, 235(3): 759-767.
32 Fouda AY, Xu Z, Narayanan SP, et al. Utility of LysM-cre and Cdh5-cre driver mice in retinal and brain research: an imaging study using tdTomato reporter mouse[J]. Invest Ophthalmol Vis Sci, 2020, 61(3): 51.
33 Gustafsson E, Brakebusch C, Hietanen K, et al. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice[J]. J Cell Sci, 2001, 114(pt 4): 671-676.
[1] Yu Yuelin,Kong Weidong. Research progress on the association between primary failure of tooth eruption and parathyroid hormone receptor 1 gene [J]. Int J Stomatol, 2023, 50(5): 573-580.
[2] Jiang Duan,Shen Daonan,Zhao Lei,Wu Yafei. Research progress on the relationship between new anti-inflammatory factor developmental endothelial locus-1 and periodontitis [J]. Int J Stomatol, 2022, 49(2): 244-248.
[3] Wu Chunlan,Tang Hua,Chen Jun. Alveolar bone morphology of anterior teeth areas in patients with high-angle skeletal Class Ⅱ open bite [J]. Int J Stomatol, 2021, 48(4): 426-432.
[4] Lei Shuang,Yu Jingjun,Tang Xiaolin. Research progress on the effects and mechanisms of Porphyromonas gingivalis on vascular endothelial cells from different tissues [J]. Int J Stomatol, 2021, 48(1): 23-28.
[5] Fu Shijin,Zeng Kan,Li Xin,Yang Jing,Wang Chenglin,Ye Ling. Preliminary study on osteoprotegerin/receptor activator of nuclear factor-κB ligand expression in mandible and femur on site selectivity of bone metastasis of lung cancer cells [J]. Int J Stomatol, 2020, 47(5): 538-546.
[6] Chen Yiyin,Liu Junqi,Li Chenghao. Effects of cleft characteristics and orthodontic treatment on alveolar bone grafting in patients with cleft lip and palate [J]. Int J Stomatol, 2020, 47(3): 345-350.
[7] Wang Linxuan,Wang Qi,Zhao Yun,Mi Fanglin. Research progress of erythropoietin-producing hepatocyte kinase receptor and ephrin ligand in alveolar bone remodeling [J]. Int J Stomatol, 2019, 46(6): 724-729.
[8] Xin Gao,Rongsheng Zeng. Research progress on osteoprotegerin in oral science [J]. Int J Stomatol, 2019, 46(3): 316-319.
[9] Yixuan Jiang,Longyi Mo,Xiaoyue Jia,Xin Xu,Chengcheng Liu. Prevention and treatment for periodontitis by phytoestrogens [J]. Inter J Stomatol, 2018, 45(5): 571-578.
[10] Wu Qi, Liu Chengcheng, Zheng Liwei, Li Jiyao, Zhou Xuedong, Xu Xin. Research progress on gut microbiota regulating bone metabolism [J]. Inter J Stomatol, 2017, 44(6): 628-635.
[11] Liu Shuang, Li Shu.. The effect of epigenetics and its regulation on periodontal disease [J]. Inter J Stomatol, 2017, 44(5): 523-527.
[12] An Ning, Tang Zhenglong. Research progress on the regulation of parathyroid hormone on the remodeling of periodontal tissues [J]. Inter J Stomatol, 2017, 44(4): 466-470.
[13] Lu Yong, Shi Bing, Wang Zhiyong, Li Hao. Clinical study on secondary alveolar bone grafting by lip side combined with palate side approach [J]. Inter J Stomatol, 2017, 44(1): 19-23.
[14] Gou Min, Cai Xiaoxiao. . Effect of implant-abutment microgap on bone tissues surrounding the necks of implants [J]. Int J Stomatol, 2015, 42(6): 733-738.
[15] Yao Yao, Pan Juli. Osteogenic potential of maxillary sinus membrane in the progress on sinus membrane elevation [J]. Inter J Stomatol, 2015, 42(4): 432-435.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .