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Effects of substance P on osteoblastic differentiation and heme oxygenase-1 in human periodontal ligament cells
Authors:Yoon-Ah Kook  Sun-Kyung Lee  Dae-Hyung Son  Kyung-Hwa Kang  Sang-Cheol Kim  Hwa-Jeong Lee  Eun-Cheol Kim
Affiliation:a Department of Orthodontics, Graduate School of Clinical Dental Science, Catholic University, Seoul, South Korea
b Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, South Korea
c Department of Orthodontics, College of Dentistry, Wonkwang University, Iksan, South Korea
d Department of Biochemistry, College of Medicine, Wonkwang University, Iksan, South Korea
e Department of Oral Pathology, College of Dentistry, Kangnung National University, Gangneung, South Korea
Abstract: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-κB 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.
Keywords:Substance P   HO-1   PDL cells   Nrf-2   Osteogenic differentiation
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