Icariin induces osteoblast proliferation, differentiation and mineralization through estrogen receptor-mediated ERK and JNK signal activation

Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats.

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“…The area of calcified nodules reflects the activation of osteoblasts and bone formation rate [23]. As shown in Figs.…”

Section: Resultsmentioning

confidence: 99%

Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats

Wang

Zhao

et al. 2017

Cell Physiol Biochem

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“…Several other studies have shown that icariin increases the levels of the bone matrix proteins ALP, COL I and OCN, which are required for matrix synthesis [28]. Moreover, numerous studies have shown that icariin promotes the formation of calcium nodules [29]. Studies have shown that icariin may be useful in the prevention of endothelial cell damage induced by reactive oxygen species [30].…”

Section: Discussionmentioning

confidence: 99%

Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway

Liu

Huang

Hao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mechanical loading plays an important role in the regulation of bone mass. However, bone cells are not always under physiological stress. In some cases, bone tissue is subjected to an overloaded mechanical environment. For example, a person who is weight training and a stevedore often experience bone pain, inflammation and other bone fatigue damage symptoms. Icariin is the major ingredient of Herba epimedii, which has been widely used for the treatment of bone injury in traditional Chinese medicine, but its mechanism remains unknown. The aim of this study was to probe the effect of icariin on the proliferation and differentiation of osteoblasts exposed to overload and to determine whether the Wnt/β-catenin signalling pathway is involved in the drug response in osteoblasts. Methods: Mouse MC3T3-E1 cells were exposed to mechanical tensile strain using a four- point bending device to create an overload damage model. An MTT assay was performed to determine the effects of icariin on MC3T3-E1 cell proliferation. The mRNA and protein levels of ALP, COL-I, OCN, RUNX2 and β-catenin were assessed using RT-PCR and immunoblotting. The protein levels of β-catenin in the MC3T3-E1 cells were also determined using fluorescence microscopy. The mineralization of osteoblasts was assessed using Alizarin Red S staining. Results: We found that icariin enhanced the proliferation of osteoblasts exposed to overload and promoted MC3T3-E1 cell differentiation and mineralization. Furthermore, the gene and protein expression levels of β-catenin and RUNX2 all increased with icariin treatment compared with those in the damage group. Conclusion: Our study suggested that icariin promotes proliferation and differentiation in osteoblasts exposed to overload. The effect of icariin on osteoblastic differentiation acted by activating the RUNX2 promoter and the Wnt/β- catenin pathway.

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“…By contrast, Luo et al (45) observed that adiponectin was able to promote osteoblast differentiation through the p38 pathway, and that adiponectin stimulated osteoblast proliferation by inducing JNK activation, but not ERK1/2, in osteoblasts. MAPK pathways serve key roles in cell proliferation, and more specifically, these pathways are considered to serve vital roles in osteoblast proliferation and differentiation (44).…”

Section: Discussionmentioning

confidence: 99%

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

Feimeng

Huang³

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Osteoporosis is a systemic skeletal disease that leads to increased bone fragility and susceptibility to fracture. Approximately 50% of postmenopausal women develop osteoporosis as a result of postmenopausal estrogen deficiency. To reduce fractures related to osteoporosis in women, previous studies have focused on therapeutic strategies that aim to increase bone formation or decrease bone resorption. However, pharmacological agents that aim to improve bone fracture susceptibility exhibit side effects. Current studies are investigating natural alternatives that possess the benefits of selective estrogen receptor modulators (SERMs) without the adverse effects. Recent studies have indicated that phytoestrogen may be an ideal natural SERM for the treatment of osteoporosis. In Chinese herbal medicine, psoralen, as the predominant substance of Psoralea corylifolia, is considered to be a phytoestrogen and is used as a remedy for osteoporosis. A number of studies have demonstrated the efficacy of psoralen in bone formation. However, the pathways and underlying molecular mechanisms that participate in psoralen-induced osteoblast formation are not well understood. In the present study, hFOB1.19 cells were treated with psoralen at different concentrations (0, 5, 10, 15 and 20 µM) for 0, 24, 36, 48 and 72 h, respectively. Reverse transcription-quantitative polymerase chain reaction and western blot assays were performed to detect glucose transporter 3 (GLUT3) expression. A cell counting kit-8 assay was used to analyze cell proliferation. In addition the effects of mitogen activated protein kinase inhibitors on extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK) and p-JNK expressions and cell proliferation were measured, as was the effect of nuclear factor (NF)-κB inhibitor on P65 and GLUT3 expressions and cell proliferation. The results indicated that psoralen stimulates hFOB1.19 cell proliferation in a dose-dependent manner (P<0.05). Phospho-ERK, p38 and JNK were markedly increased by psoralen compared with the control group (P<0.05), and the specific inhibitors of ERK (SCH772984), p38 (SB203580) and JNK (SP600125) reversed the stimulatory effects of psoralen on signal marker phosphorylation (P<0.05). The rate of psoralen-induced cell proliferation was significantly suppressed by inhibitors of ERK, JNK and p38 compared with psoralen treatment alone (P<0.05). In addition, psoralen stimulated osteoblast proliferation via the NF-κB signaling pathway. Therefore, the present findings suggest that psoralen may be a potential natural alternative to SERMs in the treatment of osteoporosis and fractures.

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Icariin induces osteoblast proliferation, differentiation and mineralization through estrogen receptor-mediated ERK and JNK signal activation

Cited by 158 publications

References 34 publications

Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats

Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats

Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

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