Effects of substance P on osteoblastic differentiation and heme oxygenase-1 in human periodontal ligament cells.
Although substance P (SP) is associated with osteoclast differentiation and bone resorption, little is known about the osteogenic differentiation-inducing effects of SP in periodontal ligament (PDL) cells. This study investigated whether PDL cells could differentiate into osteoblastic-like cells by SP. The expression of osteoblastic differentiation markers such as osteopontin (OPN), osteonectin (ON), osteocalcin (OCN) and bone sialoprotein (BSP) were evaulated by Western blotting. Additionally, SP-mediated heme oxygenase-1 (HO-1) pathways were further clarified. SP increased HO-1 and osteogenic differentiation in concentration- and time-dependent manners, as determined by OPN, ON, OCN and BSP expression. Furthermore, treatment with inhibitors of p38, ERK MAPK, and NF-kappaB abolished SP-induced osteogenic differentiation and HO-1 expression. SP-induced translocation of Nrf-2 was also observed. The combined results suggest that SP activates the stress-response enzymes HO-1 and Nrf-2, subsequently leading to upregulation of osteogenic differentiation in human PDL cells.
Department of Orthodontics, Catholic University, Seoul, South Korea.
Yoon-Ah
YA
Kook
Sun-Kyung
SK
Lee
Dae-Hyung
DH
Son
Youngho
Y
Kim
Kyung-Hwa
KH
Kang
Jin-Hyung
JH
Cho
Sang-Cheol
SC
Kim
Young-Suk
YS
Kim
Hwa-Jeong
HJ
Lee
Suk-Keun
SK
Lee
Eun-Cheol
EC
Kim
D002454:Cell Differentiation; D002461:Cell Line, Transformed; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects; D012795:Sialoglycoproteins / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D015854:Up-Regulation
D004791:Enzyme Inhibitors; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D015676:Osteonectin; D012795:Sialoglycoproteins; D015675:Osteocalcin; D053495:Osteopontin; D013373:Substance P; D051547:Heme Oxygenase-1