Wnt/β-Catenin Signaling Inhibits Osteogenic Differentiation in Human Periodontal Ligament Fibroblasts

Overview

Journal Biomimetics (Basel)

Date 2022 Dec 22

PMID 36546925

Authors

Ryoya Iizumi

Michiyo Honda

Affiliations

Soon will be listed here.

Abstract

The periodontal ligament is a collagenous tissue that is important for maintaining the homeostasis of cementum and alveolar bone. In tendon cells, Wnt/β-catenin signaling has been reported to regulate the expression level of () and () gene and maintain the tissue homeostasis, while its role in the periodontal ligament is unclear. The aim of this study was to investigate the effects of Wnt/β-catenin signaling induced by Wnt-3a stimulation on the inhibition of osteogenic differentiation of human periodontal ligament fibroblasts (HPLFs). During osteogenic differentiation of HPLFs, they formed bone nodules independently of alkaline phosphatase (ALP) activity. After stimulation of Wnt-3a, the expression of β-catenin increased, and nuclear translocation of β-catenin was observed. These data indicate that Wnt-3a activated Wnt/β-catenin signaling. Furthermore, the stimulation of Wnt-3a inhibited the bone nodule formation and suppressed the expression of osteogenic differentiation-related genes such as , and , and upregulated the gene expression of and (). may be involved in the suppression of osteogenic differentiation in HPLFs. In conclusion, Wnt/β-catenin signaling may be an important signaling pathway that inhibits the osteogenic differentiation in HPLFs by the upregulation of gene expression and downregulation of osteogenic differentiation-related genes.

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References

Yoshimoto Y, Takimoto A, Watanabe H, Hiraki Y, Kondoh G, Shukunami C . Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system. Sci Rep. 2017; 7:45010. PMC: 5361204. DOI: 10.1038/srep45010. View

Wilde J, Yokozeki M, Terai K, Kudo A, Moriyama K . The divergent expression of periostin mRNA in the periodontal ligament during experimental tooth movement. Cell Tissue Res. 2003; 312(3):345-51. DOI: 10.1007/s00441-002-0664-2. View

Rolph D, Deb M, Kanji S, Greene C, Das M, Joseph M . Ferutinin directs dental pulp-derived stem cells towards the osteogenic lineage by epigenetically regulating canonical Wnt signaling. Biochim Biophys Acta Mol Basis Dis. 2018; 1866(4):165314. PMC: 6502698. DOI: 10.1016/j.bbadis.2018.10.032. View

Afanador E, Yokozeki M, Oba Y, Kitase Y, Takahashi T, Kudo A . Messenger RNA expression of periostin and Twist transiently decrease by occlusal hypofunction in mouse periodontal ligament. Arch Oral Biol. 2005; 50(12):1023-31. DOI: 10.1016/j.archoralbio.2005.04.002. View

Lee S, Lee E, Park S, Kim J . Induction of fibrillin-2 and periostin expression in Osterix-knockdown MC3T3-E1 cells. Gene. 2016; 596:123-129. DOI: 10.1016/j.gene.2016.10.018. View

Qiu W, Chen L, Kassem M . Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells. Biochem Biophys Res Commun. 2011; 413(1):98-104. DOI: 10.1016/j.bbrc.2011.08.061. View

Kuroiwa M, Chihara K, Higashi S . Electron microscopic studies on Sharpey's fibers in the alveolar bone of rat molars. Kaibogaku Zasshi. 1994; 69(6):776-82. View

Zhang P, Chang W, Fong B, Gao F, Liu C, Al Alam D . Regulation of induced pluripotent stem (iPS) cell induction by Wnt/β-catenin signaling. J Biol Chem. 2014; 289(13):9221-32. PMC: 3979361. DOI: 10.1074/jbc.M113.542845. View

Yu B, Li Q, Zhou M . LPS‑induced upregulation of the TLR4 signaling pathway inhibits osteogenic differentiation of human periodontal ligament stem cells under inflammatory conditions. Int J Mol Med. 2019; 43(6):2341-2351. PMC: 6488177. DOI: 10.3892/ijmm.2019.4165. View

10.

Kishimoto Y, Ohkawara B, Sakai T, Ito M, Masuda A, Ishiguro N . Wnt/β-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon-derived cells. PLoS One. 2017; 12(7):e0182051. PMC: 5531628. DOI: 10.1371/journal.pone.0182051. View

11.

Lee M, Hwang H, Oh S, Roshanzadeh A, Kim J, Song J . Elevated extracellular calcium ions promote proliferation and migration of mesenchymal stem cells via increasing osteopontin expression. Exp Mol Med. 2018; 50(11):1-16. PMC: 6215840. DOI: 10.1038/s12276-018-0170-6. View

12.

Kadokura H, Yamazaki T, Masuda Y, Kato Y, Hasegawa A, Sakagami H . Establishment of a Primary Culture System of Human Periodontal Ligament Cells that Differentiate into Cementum Protein 1-expressing Cementoblast-like Cells. In Vivo. 2019; 33(2):349-352. PMC: 6506315. DOI: 10.21873/invivo.11480. View

13.

Hessle L, Johnson K, Anderson H, Narisawa S, Sali A, Goding J . Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A. 2002; 99(14):9445-9. PMC: 123160. DOI: 10.1073/pnas.142063399. View

14.

Li M, Zhang C, Yang Y . Effects of mechanical forces on osteogenesis and osteoclastogenesis in human periodontal ligament fibroblasts: A systematic review of studies. Bone Joint Res. 2019; 8(1):19-31. PMC: 6359886. DOI: 10.1302/2046-3758.81.BJR-2018-0060.R1. View

15.

Soda M, Saitoh I, Murakami T, Inada E, Iwase Y, Noguchi H . Repeated human deciduous tooth-derived dental pulp cell reprogramming factor transfection yields multipotent intermediate cells with enhanced iPS cell formation capability. Sci Rep. 2019; 9(1):1490. PMC: 6365514. DOI: 10.1038/s41598-018-37291-2. View

16.

Seo B, Miura M, Gronthos S, Bartold P, Batouli S, Brahim J . Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004; 364(9429):149-55. DOI: 10.1016/S0140-6736(04)16627-0. View

17.

Xu H, Nie E, Deng G, Lai L, Sun F, Tian H . Periostin is essential for periodontal ligament remodeling during orthodontic treatment. Mol Med Rep. 2017; 15(4):1800-1806. DOI: 10.3892/mmr.2017.6200. View

18.

Du J, Li M . Functions of Periostin in dental tissues and its role in periodontal tissues' regeneration. Cell Mol Life Sci. 2017; 74(23):4279-4286. PMC: 11107504. DOI: 10.1007/s00018-017-2645-3. View

19.

Maeda T, Hayashi S . [Morphological basis of periodontal nerve endings]. Kaibogaku Zasshi. 2000; 75(4):377-80. View

20.

Jia L, Zhang Y, Li D, Zhang W, Zhang D, Xu X . Analyses of key mRNAs and lncRNAs for different osteo-differentiation potentials of periodontal ligament stem cell and gingival mesenchymal stem cell. J Cell Mol Med. 2021; . PMC: 8256345. DOI: 10.1111/jcmm.16571. View