CKIP-1 mediates P. gingivalis-suppressed osteogenic/cementogenic differentiation of periodontal ligament cells partially via p38 signaling pathway

Xin Huang; Junhong Xiao; Huiyi Wang; Yan Peng; Heyu Liu; Li Ma; Xiaoxuan Wang; Zhengguo Cao

doi:10.1080/20002297.2023.2236427

CKIP-1 mediates P. gingivalis-suppressed osteogenic/cementogenic differentiation of periodontal ligament cells partially via p38 signaling pathway

J Oral Microbiol. 2023 Jul 20;15(1):2236427. doi: 10.1080/20002297.2023.2236427. eCollection 2023.

Authors

Xin Huang^{1

2}, Junhong Xiao¹, Huiyi Wang¹, Yan Peng¹, Heyu Liu¹, Li Ma^{1

2}, Xiaoxuan Wang^{1

2}, Zhengguo Cao^{1

2}

Affiliations

¹ State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
² Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Abstract

Objectives: Casein kinase 2 interacting protein-1 (CKIP-1) is a versatile player involved in various biological processes. However, whether CKIP-1 mediates the osteogenic/cementogenic differentiation of periodontal ligament cells (PDLCs) under Porphyromonas gingivalis (Pg) stimulation remains unknown.

Material and methods: The effect of Pg on PDLC differentiation was first verified. CKIP-1 expression in Pg-infected PDLCs or in PDL of apical periodontitis (AP) mice was detected. The changes of CKIP-1 during PDLC differentiation was also determined. PDLC differentiation capacity in CKIP-1 knockout (KO) mice and CKIP-1-silenced PDLCs with or without Pg stimulation were further studied. Inhibitor was finally applied to verify the involvement of p38 signaling pathway in PDLC differentiation.

Results: The suppression effect of Pg on PDLC differentiation was demonstrated. CKIP-1 increased in the PDL of AP mice and Pg-induced PDLCs, and decreased gradually during PDLC differentiation. Increased OSX and RUNX2 expression in PDL were observed in CKIP-1 KO mice. Also, CKIP-1 silencing facilitated and rescued Pg-inhibited PDLC differentiation. Inhibitor for p38 signaling pathway blocked CKIP-1 silencing-facilitated PDLC differentiation.

Conclusions: CKIP-1 mediated the osteogenic/cementogenic differentiation of PDLCs partially through p38 signaling pathway, which may provide evidence for the regeneration of periodontal hard tissues damaged by Pg.

Keywords: Cell differentiation; cementogenesis; osteogenesis; porphyromonas gingivalis; signal transduction.

Grants and funding

This study was supported by the National Natural Science Foundation of China to Zhengguo Cao (No. 82170963 and No. 81870776) and Xiaoxuan Wang (No. 82101022).