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Fibroblast growth factor 2 promotes matrix vesicle-mediated mineralization of human umbilical cord perivascular cells by regulating phosphate metabolism.

Sakurako Asada,Risako Chiba-Ohkuma,T. Karakida,Ryuji Yamamoto,Shun Nonoyama,Kazuhiro Gomi,T. Nagano,Yasuo Yamakoshi

Published 2025 in Journal of Oral Biosciences

ABSTRACT

OBJECTIVES We aimed to investigate the role of fibroblast growth factor 2 (FGF2) in promoting osteogenic differentiation and mineralization of human umbilical cord perivascular cells (HUCPVCs) and to elucidate the underlying molecular mechanisms, particularly the matrix vesicle-mediated mineralization pathway. METHODS HUCPVCs were cultured under osteogenic conditions with or without FGF2 in the presence of activated vitamin D3, LDN-193189, and transforming growth factor β1. Mineralization was assessed using alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, ALP staining, and calcium quantification. The selective FGF receptor inhibitor LY2874455 and exogenous tissue-non-specific ALP (TNAP) were used to evaluate the effects of FGF2. Transcriptomic analysis and expression profiling of matrix vesicle-mediated mineralization- and myofibroblast-related markers were performed using next-generation sequencing (NGS), quantitative polymerase chain reaction, and immunofluorescence staining. Extracellular pyrophosphate (PPi) was quantified using colorimetric assays. Additionally, the mineralization capacity of HUCPVCs was assessed on titanium and zirconia disks. RESULTS FGF2 significantly enhanced ALP activity and mineralization, which were abrogated by LY2874455. FGF2 upregulated TNAP and phosphate transporter 1 while suppressing ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and alpha-smooth muscle actin expression. In HUCPVCs cultured without FGF2, elevated ENPP1 and PPi levels correlated with reduced mineralization, which was rescued by supplementation with TNAP. NGS revealed upregulation of matrix vesicle-mediated mineralization-related genes. Significant mineralization was observed in HUCPVCs cultured with FGF2 on titanium and zirconia disks. CONCLUSIONS FGF2 enhances HUCPVC-mediated mineralization via dual regulation: ALP induction and ENPP1-PPi suppression. These findings support the therapeutic potential of FGF2 in bone tissue engineering and implant surface integration.

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