Wnt-GSK3/-Catenin Regulates the Differentiation of Dental Pulp Stem Cells into Bladder Smooth Muscle Cells

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2019 Feb 28

PMID 30809265

Citations 10

Authors

Wenkai Jiang

Diya Wang

Amr Alraies

Qian Liu

Bangfu Zhu

Alastair J Sloan

Longxing Ni

Bing Song

Affiliations

Soon will be listed here.

Abstract

Smooth muscle cell- (SMC-) based tissue engineering provides a promising therapeutic strategy for SMC-related disorders. It has been demonstrated that human dental pulp stem cells (DPSCs) possess the potential to differentiate into mature bladder SMCs by induction with condition medium (CM) from bladder SMC culture, in combination with the transforming growth factor-1 (TGF-1). However, the molecular mechanism of SMC differentiation from DPSCs has not been fully uncovered. The canonical Wnt signaling (also known as Wnt/-catenin) pathway plays an essential role in stem cell fate decision. The aim of this study is to explore the regulation via GSK3 and associated downstream effectors for SMC differentiation from DPSCs. We characterized one of our DPSC clones with the best proliferation and differentiation abilities. This stem cell clone has shown the capacity to generate a smooth muscle layer-like phenotype after an extended differentiation duration using the SMC induction protocol we established before. We further found that Wnt-GSK3/-catenin signaling is involved in the process of SMC differentiation from DPSCs, as well as a serial of growth factors, including TGF-1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor-homodimer polypeptide of B chain (BB) (PDGF-BB), and vascular endothelial growth factor (VEGF). Pharmacological inhibition on the canonical Wnt-GSK3/-catenin pathway significantly downregulated GSK3 phosphorylation and -catenin activation, which in consequence reduced the augmented expression of the growth factors (including TGF-1, HGF, PDGF-BB, and VEGF) as well as SMC markers (especially myosin) at a late stage of SMC differentiation. These results suggest that the canonical Wnt-GSK3/-catenin pathway contributes to DPSC differentiation into mature SMCs through the coordination of different growth factors.

Citing Articles

Crosstalk Between H-Type Vascular Endothelial Cells and Macrophages: A Potential Regulator of Bone Homeostasis.

Fan J, Xie Y, Liu D, Cui R, Zhang W, Shen M J Inflamm Res. 2025; 18:2743-2765.

PMID: 40026304 PMC: 11871946. DOI: 10.2147/JIR.S502604.

Dental pulp stem cells promote genioglossus repair and systemic amelioration in chronic intermittent hypoxia.

Zhang M, Zhang W, Lu Y, Yu L, Han X, Xu Y iScience. 2024; 27(11):111143.

PMID: 39524365 PMC: 11543914. DOI: 10.1016/j.isci.2024.111143.

Advancements in Spinal Cord Injury Repair: Insights from Dental-Derived Stem Cells.

Wen X, Jiang W, Li X, Liu Q, Kang Y, Song B Biomedicines. 2024; 12(3).

PMID: 38540295 PMC: 10968527. DOI: 10.3390/biomedicines12030683.

Effects of different signaling pathways on odontogenic differentiation of dental pulp stem cells: a review.

Zhou L, Zhao S, Xing X Front Physiol. 2023; 14:1272764.

PMID: 37929208 PMC: 10622672. DOI: 10.3389/fphys.2023.1272764.

Differential Effects of Extracellular Matrix Glycoproteins Fibronectin and Laminin-5 on Dental Pulp Stem Cell Phenotypes and Responsiveness.

Lee H, Bae A, Kim J, Kingsley K J Funct Biomater. 2023; 14(2).

PMID: 36826890 PMC: 9963712. DOI: 10.3390/jfb14020091.

References

Pittenger M, Mackay A, Beck S, Jaiswal R, Douglas R, Mosca J . Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284(5411):143-7. DOI: 10.1126/science.284.5411.143. View

Yamashita J, Itoh H, Hirashima M, Ogawa M, Yurugi T, Naito M . Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature. 2000; 408(6808):92-6. DOI: 10.1038/35040568. View

Gronthos S, Mankani M, Brahim J, Robey P, Shi S . Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000; 97(25):13625-30. PMC: 17626. DOI: 10.1073/pnas.240309797. View

Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F . Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A. 2001; 98(18):10344-9. PMC: 56963. DOI: 10.1073/pnas.181177898. View

Okamoto T, Aoyama T, Nakayama T, Nakamata T, Hosaka T, Nishijo K . Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells. Biochem Biophys Res Commun. 2002; 295(2):354-61. DOI: 10.1016/s0006-291x(02)00661-7. View

Lai J, Yoon C, Yoo J, Wulf T, Atala A . Phenotypic and functional characterization of in vivo tissue engineered smooth muscle from normal and pathological bladders. J Urol. 2002; 168(4 Pt 2):1853-7; discussion 1858. DOI: 10.1097/01.ju.0000030040.76258.5a. View

Stehr M, Adam R, Khoury J, Zhuang L, Solomon K, Peters C . Platelet derived growth factor-BB is a potent mitogen for rat ureteral and human bladder smooth muscle cells: dependence on lipid rafts for cell signaling. J Urol. 2003; 169(3):1165-70. DOI: 10.1097/01.ju.0000041501.01323.b9. View

Trowbridge H . Pulp biology: progress during the past 25 years. Aust Endod J. 2003; 29(1):5-12. DOI: 10.1111/j.1747-4477.2003.tb00485.x. View

Fukuhara S, Tomita S, Yamashiro S, Morisaki T, Yutani C, Kitamura S . Direct cell-cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro. J Thorac Cardiovasc Surg. 2003; 125(6):1470-80. DOI: 10.1016/s0022-5223(02)73610-6. View

10.

Polesskaya A, Seale P, Rudnicki M . Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell. 2003; 113(7):841-52. DOI: 10.1016/s0092-8674(03)00437-9. View

11.

de Boer J, Wang H, van Blitterswijk C . Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng. 2004; 10(3-4):393-401. DOI: 10.1089/107632704323061753. View

12.

Bieback K, Kern S, Kluter H, Eichler H . Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004; 22(4):625-34. DOI: 10.1634/stemcells.22-4-625. View

13.

Kiddoo D, Carr M, Dulczak S, Canning D . Initial management of complex urological disorders: bladder exstrophy. Urol Clin North Am. 2004; 31(3):417-26, vii-viii. DOI: 10.1016/j.ucl.2004.04.023. View

14.

Snodgrass W, Adams R . Initial urologic management of myelomeningocele. Urol Clin North Am. 2004; 31(3):427-34, viii. DOI: 10.1016/j.ucl.2004.04.001. View

15.

Soergel T, Cain M, Misseri R, Gardner T, Koch M, Rink R . Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropathic bladder. J Urol. 2004; 172(4 Pt 2):1649-51. DOI: 10.1097/01.ju.0000140194.87974.56. View

16.

Kanematsu A, Yamamoto S, Iwai-Kanai E, Kanatani I, Imamura M, Adam R . Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells. Am J Pathol. 2005; 166(2):565-73. PMC: 1602323. DOI: 10.1016/S0002-9440(10)62278-X. View

17.

McDougal W . Metabolic complications of urinary intestinal diversion. J Urol. 1992; 147(5):1199-208. DOI: 10.1016/s0022-5347(17)37517-1. View

18.

Halleux C, Sottile V, Gasser J, Seuwen K . Multi-lineage potential of human mesenchymal stem cells following clonal expansion. J Musculoskelet Neuronal Interact. 2005; 2(1):71-6. View

19.

Danielsson C, Ruault S, Basset-Dardare A, Frey P . Modified collagen fleece, a scaffold for transplantation of human bladder smooth muscle cells. Biomaterials. 2005; 27(7):1054-60. DOI: 10.1016/j.biomaterials.2005.07.027. View

20.

Zhang Y, Lin H, Frimberger D, Epstein R, Kropp B . Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder. BJU Int. 2005; 96(7):1120-5. DOI: 10.1111/j.1464-410X.2005.05741.x. View