Synergistic effect of FGF-2 and TGF-β1 on the mineralization of human umbilical cord perivascular cells

Masahiro Yabe; Takeo Karakida; Kazuo Onuma; Ryuji Yamamoto; Risako Chiba-Ohkuma; Sakurako Asada; Yasuo Yamakoshi; Kazuhiro Gomi

doi:10.1016/j.archoralbio.2023.105826

Synergistic effect of FGF-2 and TGF-β1 on the mineralization of human umbilical cord perivascular cells

Arch Oral Biol. 2023 Dec:156:105826. doi: 10.1016/j.archoralbio.2023.105826. Epub 2023 Oct 19.

Authors

Masahiro Yabe¹, Takeo Karakida², Kazuo Onuma², Ryuji Yamamoto², Risako Chiba-Ohkuma², Sakurako Asada¹, Yasuo Yamakoshi³, Kazuhiro Gomi¹

Affiliations

¹ Department of Periodontology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
² Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
³ Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. Electronic address: yamakoshi-y@tsurumi-u.ac.jp.

PMID: 37898061
DOI: 10.1016/j.archoralbio.2023.105826

Abstract

Objective: Human umbilical cord perivascular cells (HUCPVCs) are derived from the human umbilical cord perivascular tissue and are expected to replace mesenchymal stromal cells in the future. We investigated the synergistic effects of fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 1 (TGF-β1) on HUCPVC mineralization.

Design: We prepared HUCPVCs with (FGF(+)HUCPVCs) or without FGF-2 (FGF(-)HUCPVCs) in the presence of activated vitamin D₃, a bone morphogenic protein inhibitor, and TGF-β1. We examined the cell proliferative capacity, expression of various hard tissue-forming cell gene markers, and mineralization induction ability and identified the crystalline phases of the mineralized nodules.

Results: FGF(+)HUCPVCs exhibited higher intracellular alkaline phosphatase (ALP) gene expression and ALP activity, and their cell proliferation rate was higher than that of FGF(-)HUCPVCs. The expression levels of osteoblast marker genes increased in FGF(+)HUCPVCs, whereas those of elastic fiber and muscle cell markers increased in FGF(-)HUCPVCs. The expression of genes related to matrix vesicle-mediated mineralization was increased in FGF(+)HUCPVCs. While FGF(-)HUCPVCs displayed myofibroblast-like properties and could not induce mineralization, FGF(+)HUCPVCs demonstrated the ability to produce mineralized nodules. The resulting mineralized nodules consisted of hydroxyapatite as the major phase and minor amounts of octacalcium phosphate. The mineralized nodules exhibited the morphological characteristics of bone hydroxyapatite, composed of fibrous hydroxyapatite nanorods and polycrystalline sheets.

Conclusion: We found that FGF-2 synergizes with TGF-β1 and is a key factor in the differentiation of HUCPVCs into osteoblast-like cells. Thus, HUCPVCs can potentially serve as a new stem cell source for future bone regeneration and dental treatments.

Keywords: Bone; Fibroblast growth factor 2; Human umbilical cord perivascular cells; Hydroxyapatite; Stem cells; Transforming growth factor-beta.

MeSH terms

Cell Differentiation
Fibroblast Growth Factor 2* / pharmacology
Humans
Hydroxyapatites / pharmacology
Mesenchymal Stem Cells*
Transforming Growth Factor beta1 / metabolism
Transforming Growth Factor beta1 / pharmacology
Umbilical Cord

Substances

Fibroblast Growth Factor 2
Transforming Growth Factor beta1
Hydroxyapatites