Next Article in Journal
Intratumor Heterogeneity and Therapy Resistance: Contributions of Dormancy, Apoptosis Reversal (Anastasis) and Cell Fusion to Disease Recurrence
Previous Article in Journal
Genomics-Enabled Analysis of Puroindoline b2 Genes Identifies New Alleles in Wheat and Related Triticeae Species
Open AccessArticle

Carboxy-Terminal Cementum Protein 1-Derived Peptide 4 (cemp1-p4) Promotes Mineralization through wnt/β-catenin Signaling in Human Oral Mucosa Stem Cells

1
Laboratorio de Biología Periodontal, Facultad de Odontología, Universidad Nacional Autónoma de México, CDMX 04510, Mexico
2
Departamento de Bioquímica, Facultad de Medicina, UNAM, Universidad Nacional Autónoma de México, CDMX 04510, Mexico
3
Instituto de Oftalmología Conde de Valenciana, CDMX 06800, Mexico
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1307; https://doi.org/10.3390/ijms21041307
Received: 20 January 2020 / Revised: 11 February 2020 / Accepted: 12 February 2020 / Published: 15 February 2020
(This article belongs to the Section Materials Science)
Human cementum protein 1 (CEMP1) is known to induce cementoblast and osteoblast differentiation and alkaline phosphatase (ALP) activity in human periodontal ligament-derived cells in vitro and promotes bone regeneration in vivo. CEMP1′s secondary structure analysis shows that it has a random-coiled structure and is considered an Intrinsic Disordered Protein (IDP). CEMP1′s short peptide sequences mimic the biological capabilities of CEMP1. However, the role and mechanisms of CEMP1′s C-terminal-derived synthetic peptide (CEMP1-p4) in the canonical Wnt/β-catenin signaling pathway are yet to be described. Here we report that CEMP1-p4 promotes proliferation and differentiation of Human Oral Mucosa Stem Cells (HOMSCs) by activating the Wnt/β-catenin pathway. CEMP1-p4 stimulation upregulated the expression of β-catenin and glycogen synthase kinase 3 beta (GSK-3B) and activated the transcription factors TCF1/7 and Lymphoid Enhancer binding Factor 1 (LEF1) at the mRNA and protein levels. We found translocation of β-catenin to the nucleus in CEMP1-p4-treated cultures. The peptide also penetrates the cell membrane and aggregates around the cell nucleus. Analysis of CEMP1-p4 secondary structure revealed that it has a random-coiled structure. Its biological activities included the induction to nucleate hydroxyapatite crystals. In CEMP1-p4-treated HOMSCs, ALP activity and calcium deposits increased. Expression of Osterix (OSX), Runt-related transcription factor 2 (RUNX2), Integrin binding sialoproptein (IBSP) and osteocalcin (OCN) were upregulated. Altogether, these data show that CEMP1-p4 plays a direct role in the differentiation of HOMSCs to a “mineralizing-like” phenotype by activating the β-catenin signaling cascade. View Full-Text
Keywords: cementum; peptide; β-catenin; cell differentiation; CEMP1-p4; mineralization; stem cells cementum; peptide; β-catenin; cell differentiation; CEMP1-p4; mineralization; stem cells
Show Figures

Graphical abstract

MDPI and ACS Style

Arroyo, R.; López, S.; Romo, E.; Montoya, G.; Hoz, L.; Pedraza, C.; Garfias, Y.; Arzate, H. Carboxy-Terminal Cementum Protein 1-Derived Peptide 4 (cemp1-p4) Promotes Mineralization through wnt/β-catenin Signaling in Human Oral Mucosa Stem Cells. Int. J. Mol. Sci. 2020, 21, 1307.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop