Chrysosplenetin promotes osteoblastogenesis of bone marrow stromal cells via Wnt/β-catenin pathway and enhances osteogenesis in estrogen deficiency-induced bone loss

Abstract

Background Chrysosplenetin is an O-methylated flavonol compound isolated from the plant Chamomilla recutita and Laggera pterodonta . The aim of our research is to evaluate the function of Chrysosplenetin on osteogenesis of human-derived bone marrow stromal cells (hBMSCs) and inhibition of estrogen deficiency-induced osteoporosis via the Wnt/β-catenin signaling pathway. Method hBMSCs are cultured and treated by Chrysosplenetin in the absence or presence of Wnt inhibitor dickkopf-related protein 1 (DKK1) or bone morphogenetic protein 2 (BMP2) antagonist Noggin. RT-qPCR is taken to identify the genetic expression of target genes of Wnt/β-catenin pathway and osteoblast-specific markers. The situation of β-catenin is measured by western blot and immunofluorescence staining. An ovariectomized (OVX) mouse model is set up to detect the bone loss suppression by injecting Chrysosplenetin . Micro-CT and histological assay are performed to evaluate the protection of bone matrix and osteoblast number. Serum markers related with osteogenesis are detected by ELISA. Results In the present study, it is found that Chrysosplenetin time-dependently promoted proliferation and osteoblastogenesis of hBMSCs reaching its maximal effects at a concentration of 10 μM. The expressions of target genes of Wnt/β-catenin pathway and osteoblast-specific marker genes are enhanced by Chrysosplenetin treatment. Furthermore, the phosphorylation of β-catenin is decreased, and nuclear translocation of β-catenin is promoted by Chrysosplenetin . Osteogenesis effects mentioned above are founded to be blocked by DKK1 or BMP2 antagonist Noggin. In vivo study reveals that Chrysosplenetin prevents estrogen deficiency-induced bone loss in OVX mice detected by Micro-CT, histological analysis, and ELISA . Conclusions Our study demonstrates that Chrysosplenetin improves osteoblastogenesis of hBMSCs and osteogenesis in estrogen deficiency-induced bone loss by regulating Wnt/β-catenin pathway. Electronic supplementary material The online version of this article (10.1186/s13287-019-1375-x) contains supplementary material, which is available to authorized users.

Exercise improves bone formation by upregulating the Wnt3a/β-catenin signalling pathway in type 2 diabetic mice

“…Park et al [ 35 ] verified that the number of OBs differentiated by BMSCs in T2DM mice and the bone formation thereof decreased, and many signalling pathways or key molecules have a significant regulatory function in the process. Wnt3a/β-catenin is a key pathway regulating bone formation, and can regulate OB differentiation and osteogenic capacity [ 13 , 21 ]. As a key subtype of Wnt proteins, activated Wnt3a leads to the phosphorylation of β-catenin, which activates the expression of downstream target genes Runx2, Osx, and others, while regulating OB differentiation and bone formation [ 44 ].…”

Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats

“…[ 36 ] Studies have demonstrated that [ 37 ] GC excess exerted its detrimental effect on bone formation partially due to inhibition of Wnt-signaling, and that activation of Wnt/β-catenin signaling significantly stimulated proliferation and osteogenesis in mesenchymal cells. [ 8 , 38 ] We, therefore, speculate that the effects of lithium on GC-treated rats may have contributed to the activation of Wnt/β-catenin signaling, although no further detection of this pathway in this study. However, further study on the mechanism of lithium in bone metabolism will be undertaken both in vivo and in vitro .…”

Troxerutin Stimulates Osteoblast Differentiation of Mesenchymal Stem Cell and Facilitates Bone Fracture Healing

“…A number of evidence have demonstrated that this signaling plays key regulatory roles in cellular differentiation and matrix formation during skeletal development and formation ( Chen et al, 2007 ; Aline et al, 2013 ). The activation of canonical Wnt/β-catenin signaling cascade is significant for the bone formation and regeneration ( Duan and Bonewald, 2016 ; Tian et al, 2018 ); and the agonist of this signaling has been proved to accelerate the bone repair in the early stage of fracture healing ( Hong, et al, 2019 ). In this study, we found that the expression of intranuclear β-catenin and several downstream target genes of Wnt/β-catenin was up-regulated by TRX, indicating the activation of Wnt/β-catenin signaling in TRX-mediated osteogenesis.…”