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Jagged1 inhibits osteoprotegerin expression by human periodontal ligament cells
Author(s) -
Manokawinchoke J.,
Sumrejkanchanakij P.,
Subbalekha K.,
Pavasant P.,
Osatha T.
Publication year - 2016
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12357
Subject(s) - rankl , osteoprotegerin , chemistry , microbiology and biotechnology , periodontal fiber , osteoclast , notch signaling pathway , stromal cell , receptor , activator (genetics) , medicine , biology , dentistry , biochemistry
Background and Objective Notch signaling regulates bone homeostasis. The present study investigated the effect of Jagged1 on osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappa‐B ligand ( RANKL ) expression in human periodontal ligament stromal ( hPDL ) cells. Material and Methods hPDL cells were seeded on to indirect immobilized Jagged1 surfaces. OPG expression was determined using real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay . Lentiviral small hairpin RNA particles against NOTCH 2 were employed to inhibit NOTCH 2 expression. Osteoclast formation was evaluated using RAW 264.7 cells. An influence of exogenous OPG on osteogenic differentiation was determined by real‐time polymerase chain reaction and Alizarin Red S staining. Results Jagged1 significantly enhanced HES 1 and HEY 1 mRNA expression in a dose‐dependent manner. Furthermore, OPG mRNA and protein levels dramatically decreased upon exposing hPDL cells to Jagged1. However, RANKL mRNA levels were not significantly different. There was also no difference in M‐ CSF and MCP ‐1 mRNA expression. A γ‐secretase inhibitor and cycloheximide treatment rescued Jagged1‐attenuated OPG expression. Furthermore, sh NOTCH 2 overexpressing hPDL cells did not exhibit a decrease in OPG expression upon exposure to Jagged1, implying the involvement of NOTCH 2 in the regulatory mechanism. Culturing RAW 264.7 cells with conditioned medium from Jagged1‐treated hPDL cells enhanced osteoclast formation compared with those cultured with conditioned medium of the control group. Lastly, OPG treatment did not influence osteogenic differentiation by hPDL cells. Conclusion These results suggest that Jagged1 activates Notch signaling in hPDL cells, leading to decreased OPG expression. This may imply an indirect role of Jagged1 on the regulation of osteoclast differentiation via hPDL cells.