High-Density Culture and Lipopolysaccharide Cooperatively Activate TAK1–MAPK Signaling to Promote Osteogenic Differentiation in Human Dental Pulp Stem Cells
- 1Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8549, Japan
- 2Department of Endodontics, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo 102-8159, Japan
Abstract
Human dental pulp stem cells (hDPSCs) are promising for regenerative medicine because of their multipotent differentiation capacity and ease of isolation from extracted teeth. We previously reported that high-density culture enhanced their osteogenic potential; however, the inflammatory environment at the transplantation site may influence osteogenic differentiation. This study investigated the effects of lipopolysaccharide (LPS) on the osteogenic differentiation of hDPSCs cultured at high density. hDPSCs were seeded at either low or high density and stimulated with LPS. High-density culture increased focal adhesion kinase (FAK) phosphorylation, a well-established marker of integrin signaling activation, and enhanced osteogenic differentiation. Under high-density culture conditions, LPS further increased the expression of the osteogenic markers bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2) and promoted mineralized nodule formation. Moreover, LPS stimulation induced the phosphorylation of transforming growth factor-β-activated kinase-1 (TAK1), p38 and c-Jun N-terminal kinase (JNK) exclusively under high-density culture conditions. TAK1 inhibition suppressed the phosphorylation of p38 and JNK and reduced BMP2 and RUNX2 expression. TAK1 phosphorylation was attenuated by a FAK inhibitor in LPS-stimulated hDPSCs cultured at high density. These findings suggest that FAK signaling associated with high-density culture facilitates LPS-induced TAK1–MAPK activation, contributing to increased BMP2 and RUNX2 expression and enhanced mineralized nodule formation in hDPSCs.
Related
- BIRC3 facilitates osteogenic differentiation of bone marrow mesenchymal stem cells via NGFR/β-catenin signalling axis
- High-Calorie Diet Aggravates Lipopolysaccharide-Induced Pulmonary Inflammation in Juvenile Mice: Association of Acetate-Mediated Macrophage Polarization with AMPK/YAP Signaling
- A stratified cell sheet platform coordinating dual osteogenic and chondrogenic differentiation for osteochondral tissue engineering.
- Machine-learning-assisted target prioritization and experimental validation of the neoeriocitrin–mTOR axis in impaired osteogenic differentiation
- ITGBL1 inhibits obesity and osteoporosis by maintaining adipogenic and osteogenic differentiation balance via the NEDD4–PPARγ–RUNX2 axis
BibTeX
@article{pwint2026highdensity,
title = {{High-Density Culture and Lipopolysaccharide Cooperatively Activate TAK1–MAPK Signaling to Promote Osteogenic Differentiation in Human Dental Pulp Stem Cells}},
author = {Khaing Nyein Pwint and Nobuyuki Kawashima and Yamato Okada and Sonoko Noda and Takashi Okiji and Yoshio Yahata},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219515},
url = {https://www.mdpi.com/1422-0067/27/21/9515},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - High-Density Culture and Lipopolysaccharide Cooperatively Activate TAK1–MAPK Signaling to Promote Osteogenic Differentiation in Human Dental Pulp Stem Cells
AU - Khaing Nyein Pwint
AU - Nobuyuki Kawashima
AU - Yamato Okada
AU - Sonoko Noda
AU - Takashi Okiji
AU - Yoshio Yahata
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219515
UR - https://www.mdpi.com/1422-0067/27/21/9515
AB - Human dental pulp stem cells (hDPSCs) are promising for regenerative medicine because of their multipotent differentiation capacity and ease of isolation from extracted teeth. We previously reported that high-density culture enhanced their osteogenic potential; however, the inflammatory environment at the transplantation site may influence osteogenic differentiation. This study investigated the effects of lipopolysaccharide (LPS) on the osteogenic differentiation of hDPSCs cultured at high density. hDPSCs were seeded at either low or high density and stimulated with LPS. High-density culture increased focal adhesion kinase (FAK) phosphorylation, a well-established marker of integrin signaling activation, and enhanced osteogenic differentiation. Under high-density culture conditions, LPS further increased the expression of the osteogenic markers bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2) and promoted mineralized nodule formation. Moreover, LPS stimulation induced the phosphorylation of transforming growth factor-β-activated kinase-1 (TAK1), p38 and c-Jun N-terminal kinase (JNK) exclusively under high-density culture conditions. TAK1 inhibition suppressed the phosphorylation of p38 and JNK and reduced BMP2 and RUNX2 expression. TAK1 phosphorylation was attenuated by a FAK inhibitor in LPS-stimulated hDPSCs cultured at high density. These findings suggest that FAK signaling associated with high-density culture facilitates LPS-induced TAK1–MAPK activation, contributing to increased BMP2 and RUNX2 expression and enhanced mineralized nodule formation in hDPSCs.
SN - 1422-0067
ER -