Lgr4 Expression in Osteoblastic Cells Is Suppressed by Hydrogen Peroxide Treatment

Abstract

LGR4 is expressed in bone and has been shown to be involved in bone metabolism. Oxidative stress is one of the key issues in pathophysiology of osteoporosis. However, the link between Lgr4 and oxidative stress has not been known. Therefore, effects of hydrogen peroxide on Lgr4 expression in osteoblasts were examined. Hydrogen peroxide treatment suppressed the levels of Lgr4 mRNA expression in an osteoblastic cell line, MC3T3-E1. The suppressive effects were not obvious at 0.1 mM, while 1 mM hydrogen peroxide suppressed Lgr4 expression by more than 50%. Hydrogen peroxide treatment suppressed Lgr4 expression within 12 h and this suppression lasted at least up to 48 h. Hydrogen peroxide suppression of Lgr4 expression was still observed in the presence of a transcription inhibitor but was no longer observed in the presence of a protein synthesis inhibitor. Although Lgr4 expression in osteoblasts is enhanced by BMP2 treatment as reported before, hydrogen peroxide treatment suppressed Lgr4 even in the presence of BMP2. Finally, hydrogen peroxide suppressed Lgr4 expression in primary cultures of osteoblasts similarly to MC3T3-E1 cells. These date indicate that hydrogen peroxide suppresses Lgr4 expression in osteoblastic cells. J. Cell. Physiol. 232: 1761-1766, 2017. © 2016 Wiley Periodicals, Inc.

Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis

“…However, the correlation between LGR4 and oxidative stress remained unknown. Pawaputanon Na et al explored that the treatment of hydrogen peroxide decreased the expression of LGR4 in osteoblastic cells ( Pawaputanon Na Mahasarakham et al, 2017 ). Rspo1-LGR4 axis protected hepatocytes against acute injury by suppressing NF-κB-p65 via Wnt3a/β-catenin pathway ( Li Z. et al, 2019 ).…”

The Role of LGR4 (GPR48) in Normal and Cancer Processes

“…Another study used the MCT3-E1 cell line to show that RSPO2-LGR4 signaling not only induced osteogenesis but also inhibited osteoclastogenesis through the Wnt signaling pathway [78]. In osteoblastic cells, LGR4 expression is induced by the BMP protein during osteoblast differentiation and activation [79,80]. Opposing to this induction, Cong et al 2017 showed that microRNA-34c can inhibit LGR4 transcription, thus inducing osteoclast differentiation, regulating NF-κB and GSK3β signaling during that process [32].…”