Stress response in periodontal ligament stem cells may contribute to bisphosphonateassociated osteonecrosis of the jaw: A gene expression array analysis.
Mol Med Rep
; 22(3): 2043-2051, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-32705175
ABSTRACT
Gene expression alterations in periodontal ligament stem cells (PDLSCs) during bisphosphonate (BP) usage and the transcriptomic mechanism underlying BPrelated osteonecrosis of the jaw have not been fully elucidated. In the present study, human PDLSCs were isolated from adults with no history of periodontal disease, and subsequently incubated and treated with zoledronate on days 3 and 5. Subsequently, PDLSCs from all timepoints were screened using an Affymetrix Gene Expression Array. Limma differential expression analysis was performed on a normalized gene expression matrix, followed by cluster analysis, pathway and network analyses. Overall, 906 genes (352 upregulated and 554 downregulated) exhibited differential expression levels between days 0 and 5, and these were termed slowresponse genes. These slowresponse genes were enriched in cellular stress response signaling pathways (upregulated genes), as well as proliferation and ossificationassociated signaling pathways (downregulated genes). Furthermore, 168 (day 3 vs. 0) and 105 (day 5 vs. 3) genes were differentially expressed between adjacent timepoints. These genes were also enriched in stress response and proliferationassociated signaling pathways, but not in ossificationassociated signaling pathways. Poly(ADPribose) polymerase 1 (PARP1) and CYLD lysine 63 deubiquitinase (CYLD) had the most proteinprotein interaction partners among the slowresponse genes and were connected with both stress (e.g. caspase1) and ossificationassociated genes [e.g. secreted phosphoprotein 1 and collagen type I α1 chain (COL1A1)]. BP treatment induced stress responselike transcriptional alterations in PDLSCs, followed by inhibition of proliferation and ossification. These alterations may contribute to the onset of jaw osteonecrosis. PARP1 and CYLD may be two key genes involved in this pathological procedure.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Periodontal Ligament
/
Gene Expression Profiling
/
Bisphosphonate-Associated Osteonecrosis of the Jaw
/
Poly (ADP-Ribose) Polymerase-1
/
Deubiquitinating Enzyme CYLD
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2020
Document type:
Article