ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis

Abstract

Reports of the ameliorative effect of angelicin on sex hormone deficiency-induced osteoporosis have highlighted this compound as a candidate for the treatment of osteoporosis. However, the molecular mechanisms of action of angelicin on osteoblast differentiation have not been thoroughly researched. The aim of the present study was to evaluate the effect of angelicin on the proliferation, differentiation and mineralization of rat calvarial osteoblasts using a Cell Counting Kit-8, alkaline phosphatase activity and the expression of osteogenic genes and proteins. Treatment with angelicin promoted the proliferation, matrix mineralization and upregulation of osteogenic marker genes including collagen type I α 1 and bone γ-carboxyglutamate in fetal rat calvarial osteoblasts. Furthermore, angelicin promoted the expression of β-catenin and runt related transcription factor 2, which serve a vital role in the Wnt/β-catenin signaling pathway. Consistently, the osteogenic effect of angelicin was attenuated by the use of a Wnt inhibitor. Moreover, angelicin increased the expression of estrogen receptor α (ERα), which also serves a key role in osteoblast differentiation. Taken together, these results demonstrated that angelicin may promote osteoblast differentiation through activation of ERα and the Wnt/β-catenin signaling pathway.

Angelicin—A Furocoumarin Compound With Vast Biological Potential

“…Hence, potential compounds that could upregulate the body's estrogen levels are needed. The treatment of MC3T3-E1 cells and primary rat osteoblast cells with angelicin increased the expression of ERa protein (Ge et al, 2018;Ge et al, 2019). A similar increase in ERa by angelicin in the grey matter of ventral and dorsal horns were also reported in adult male C57BL/6 mice that had suffered spinal cord injury (Li et al, 2017a).…”

“…To determine the involvement of Wnt/b-catenin signaling pathway, the cells were co-treated with both angelicin and DKK-1, an antagonist to the pathway. The results obtained revealed that DKK-1 successfully attenuated the effect angelicin had on the cells (Ge et al, 2019). Besides that, Zhang and Ta (2017) also studied the effect of angelicin on TGF-b1 reporter gene activity using transfected HEK293T cells.…”

“…In both the primary bone marrow mesenchymal stem cells (BMSC) (obtained from 4 week old C57BL/6 mice) as well as primary rat osteoblasts cells (obtained from female Winstar rats) that were treated with angelicin, significant increases in BMP-2, Runx2, OCN, and b -catenin were reported in multiple studies (Wang et al, 2017b;Ge et al, 2019). Using immunofluorescence staining, it was also revealed that not only was b-catenin upregulated by angelicin, there was also an increase in b-catenin translocation into the nucleus after treatment (Ge et al, 2019). To determine the involvement of Wnt/b-catenin signaling pathway, the cells were co-treated with both angelicin and DKK-1, an antagonist to the pathway.…”

“…In the year 2014, when angelicin was tested against primary rat osteoblastic cells obtained from newborn Winstar rats, it was initially reported that angelicin had no effect on cell proliferation or alkaline phosphatase (ALP) activity (Li et al, 2014). However, in a recent paper, Ge et al (2019) had demonstrated that angelicin was able to not only increase the proliferation of osteoblast but also to induce the expression of alkaline phosphatase (ALP) after 7 days of treatment while the matrix mineralization of the cells can be seen on the 12 th day of treatment with angelicin. Similar observation of increased cell proliferation, ALP activity and mineralization of osteoblasts by angelicin were reported in MC3T3-E1 (mouse osteoblast precursor) cells and primary bone marrow mesenchymal stem cells (BMSC) with the exception that BMSC cells did not experience any changes in cell proliferation (Wang et al, 2017b;Ge et al, 2018).…”

Angelicin Alleviates Post-Trauma Osteoarthritis Progression by Regulating Macrophage Polarization via STAT3 Signaling Pathway

“…Angelica is gaining ground all over the world, including Europe, North American and Southeast Asia. In folk medicine, angelica is believed as an anti-inflammatory, anti-aging medicine with wide use ( Wei et al, 2016 ; Ge et al, 2019 ). Angelicin is isolated from Angelica Sinensis considered as an anti-frostbite, analgesia, hemostasis active ingredients.…”