Geniposide Alleviates Glucocorticoid-Induced Inhibition of Osteogenic Differentiation in MC3T3-E1 Cells by ERK Pathway

Abstract

Glucocorticoid (GC) therapy is the leading cause of secondary osteoporosis and the therapeutic and preventative drugs for GC-induced osteoporosis are limited. In this study, we investigated the protective effects of geniposide on dexamethasone (DEX)-induced osteogenic inhibition in MC3T3-E1 cells. The results showed that there was no obvious toxicity on MC3T3-E1 cells when geniposide was used at the doses ranging from 1 to 75 μM. In DEX-treated MC3T3-E1 cells, geniposide promoted the alkaline phosphatase (ALP) activity and the mineralization. In addition, geniposide also significantly increased the mRNA and protein expression of osteopontin (OPN), Runt-related transcription factor 2 (Runx2), and Osterix (Osx) in DEX-treated MC3T3-E1 cells. Furthermore, geniposide activated ERK pathway in DEX-treated MC3T3-E1 cells. The ERK activation inhibitor U0126 and glucagon-like peptide-1 (GLP-1) receptor antagonist exendin 9-39 abolished the geniposide-induced activation of ERK and inhibited the protective effect of geniposide. Taken together, our study revealed that geniposide alleviated GC-induced osteogenic suppression in MC3T3-E1 cells. The effect of geniposide was at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for GC-induced osteoporosis.

Cycloastragenol protects against glucocorticoid‐induced osteogenic differentiation inhibition by activating telomerase

“…ALP activity and mineralization are respectively recognized as the early and late markers of osteogenic differentiation in osteoblast. ALP is generated by osteoblasts and conveyed to the extracellular matrix, resulting in the generation of hydroxyapatite, which implies that osteogenic differentiation is initiated in the first stage (Liu et al, 2019; Ozeki et al, 2008; Xie et al, 2019). In the second stage, mineralization occurred in the extracellular matrix and united to calcium nodules (Wang, Olson, Cheng, Guo, & Wang, 2012), which is known as a mark of osteoblast differentiation and maturation.…”

“…BCIP/NBT solution was applied for the ALP staining. Briefly, cells were washed and fixed according to the previous study (Xie et al, 2019) and then BCIP/NBT solution was applied to treat the cells in dark for 15–30 min and the response was terminated with ultrapure water, and plates were dried and taken photos.…”

eIF2α signaling regulates autophagy of osteoblasts and the development of osteoclasts in OVX mice

“…MC3T3-E1 cells were obtained from Chinese Academy of Sciences Cell Bank. MC3T3-E1 cells differentiation were initiated in α-MEM containing 10% FBS, 100 U/mL penicillin, 100 μg/mL streptomycin, 10 mM β-glycerophosphate, and 50 μg/mL ascorbic acid 22,23 . ALP and Alizarin Red S staining was conducted to confirm osteoblasts before following experiment.…”

The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment

“…Furthermore, geniposide also significantly increased the expression of osteogenic genes of OPN, Runx2 and Osterix (Osx) in MC3T3-E1 cells treated with dexamethasone. GLP-1RA (geniposide) might be a potential therapeutic agent for GIOP ( Xie et al, 2019 ). Yang et al (2019) further verified our results by animal experiment.…”