Title:FBLN5 was Regulated by PRDM9, and Promoted Senescence and
Osteogenic Differentiation of Human Periodontal Ligament Stem Cells
Volume: 19
Issue: 3
Author(s): Mengyao Zhao, Rong Rong, Chen Zhang, Haoqing Yang, Xiao Han, Zhipeng Fan*, Ying Zheng*Jianpeng Zhang*
Affiliation:
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and
Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China
- Department of
Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
- Department of
Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
Keywords:
Periodontal ligament stem cells (PDLSCs), FBLN5, PRDM9, senescence, osteogenic differentiation, mitogenactivated protein kinase (MAPK), signaling pathway.
Abstract:
Objectives: Periodontal ligament stem cells (PDLSCs) are ideal seed cells for periodontal tissue
regeneration. Our previous studies have indicated that the histone methyltransferase PRDM9 plays an
important role in human periodontal ligament stem cells (hPDLSCs). Whether FBLN5, which is a downstream
gene of PRDM9, also has a potential impact on hPDLSCs is still unclear.
Methods: Senescence was assessed using β-galactosidase and Enzyme-linked immunosorbent assay
(ELISA). Osteogenic differentiation potential of hPDLSCs was measured through Alkaline phosphatase
(ALP) activity assay and Alizarin red detection, while gene expression levels were evaluated using western
blot and RT-qPCR analysis.
Results: FBLN5 overexpression promoted the osteogenic differentiation and senescence of hPDLSCs.
FBLN5 knockdown inhibited the osteogenic differentiation and senescence of hPDLSCs. Knockdown of
PRDM9 decreased the expression of FBLN5 in hPDLSCs and inhibited senescence of hPDLSCs. Additionally,
both FBLN5 and PRDM9 promoted the expression of phosphorylated p38 MAPK, Erk1/2 and
JNK. The p38 MAPK pathway inhibitor SB203580 and the Erk1/2 pathway inhibitor PD98059 have the
same effects on inhibiting the osteogenic differentiation and senescence of hPDLSCs. The JNK pathway
inhibitor SP600125 reduced the senescence of hPDLSCs.
Conclusion: FBLN5 promoted senescence and osteogenic differentiation of hPDLSCs via activation of
the MAPK signaling pathway. FBLN5 was positively targeted by PRDM9, which also activated the
MAPK signaling pathway.
