NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

Yao, Zhenqiang; Li, Yanyun; Xi, Yin; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F.

doi:10.1002/jbmr.2108

Cited by 56 publications

(85 citation statements)

References 49 publications

(72 reference statements)

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“…Among them, NF-kB is a well-known molecule involved in various metastatic bone diseases [25]. It has been reported that NF-kB signaling pathway is an important Effects of resveratrol on postmenopausal osteoporosis mediator in osteoblast differentiation [26,27]. Previous studies also reported that constitutive inhibition of NF-kB in Saos2 cells could increase the expression of osteoblast specific matrix protein collagen I and promote osteoblast differentiation [28,29].…”

Section: Discussionmentioning

confidence: 98%

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway

Feng¹,

Liu²,

Ma³

et al. 2014

ABBS

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Postmenopausal osteoporosis severely jeopardizes human health. Seeking for therapeutic drugs without side effects is of great necessity. Our study was designed to investigate whether resveratrol, an agonist of SIRT1, could have favorable effect on osteoporosis and to explore the underlying mechanisms. Rat osteoporosis model (ovariectomy group, OVX) was established by bilateral ovariectomy. respectively; P < 0.05). Serum markers alkaline phosphatase (ALP) and osteocalcin were moderately restored by resveratrol. Moreover, resveratrol improved bone structure in OVX rats, demonstrated by hematoxylin-eosin staining and micro-computed tomographic results. In vitro results revealed that resveratrol promoted osteoblast differentiation of bone marrow mesenchymal stromal cells, evidenced by the increase of ALP generation and mRNA expression of collagen 1 (P < 0.05; RES MD , RES HD vs. control group). SIRT1 gene silencing by siRNA transfection blocked these beneficial effects of resveratrol (P < 0.05; RES 1 SIRT1 KD vs. RES HD ).Western blot results showed that resveratrol activated SIRT1 and subsequently suppressed the activity of NF-kB with decreased expression level of p-IkBa and NF-kB p65 (P < 0.05). Our findings verified the effects of specific dosed resveratrol on postmenopausal osteoporosis through osteoblast differentiation via SIRT1-NF-kB signaling pathway. This study suggested the therapeutic potential of resveratrol against osteoporosis and stressed the importance of effective doses.

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Section: Discussionmentioning

confidence: 98%

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway

Feng¹,

Liu²,

Ma³

et al. 2014

ABBS

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“…Apoptosis of osteoblasts can increase the generation of cancellous bone, and previous research findings revealed that apoptosis in mice with diabetes was evidently increased. The NF-κB pathway of osteoclasts has already been widely studied (34). RANKL, TNF-α or IL-1 activated NF-κB signal pathway can induce differentiation gene expression of osteoclasts, lengthen the life of osteoclasts and increase bone absorption (35).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

2017

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Abstract. The aim of the present study was to determine the protective effects of resveratrol on a rat model of osteoporosis and examine the associated mechanisms of its action. Rats were randomized into the following groups: Control, osteoporosis, osteoporosis + low-dose resveratrol, osteoporosis + middle-dose resveratrol and osteoporosis + high-dose resveratrol groups. Resveratrol treatment was administered 7 days after surgery for 8 weeks. ELISA assay was used to analyze alkaline phosphatase (ALP) and osteocalcin (OC) protein levels. Western blotting was performed to assess the protein expression of sirtuin 1 (SIRT1), nuclear factor (NF)-κB and NF-κB inhibitor (IkB) α. In the present study, the results indicated that resveratrol markedly improved the bone mineral density value, femoral porosity and bone mechanical tests in osteoporosis rats. Administration of resveratrol significantly decreased the serum levels of ALP and OC in rats with osteoporosis. Finally, treatment with resveratrol significantly promoted the protein expression of SIRT1, suppressed NF-κB and activated the IkBα protein expression in rats with osteoporosis. In conclusion, treatment with resveratrol significantly improved the final body weight of the osteoporosis rats via the SIRT1-NF-κB signaling pathway. The present study suggested that resveratrol exerted a protective effect on osteoporosis through activation of the SIRT1-NF-κB signaling pathway in rats.

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“…MAPK, mitogen-activated protein kinase; SCH772984, ERK inhibitor; SB203580, P38 inhibitor; SP600125, JNK inhibitor; ERK, extracellular signal-related kinase; JNK, c-Jun N-terminal kinase; GLUT3, glucose transporter 3; P-, phosphorylated; CCK-8, cell counting kit-8. NF-κB knockout mice exhibit bone disorder (32). In the majority of cells, NF-κB is present as a latent-form in the cytoplasm and stimulates the transcription of target genes in the nucleus (33).…”

Section: Hfob119 Cell Proliferation Depends On Nk-κb-mapk Signalingmentioning

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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NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

Cited by 56 publications

References 49 publications

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

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

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NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

Cited by 56 publications

References 49 publications

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-&kappa;B signaling pathway

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-&kappa;B signaling pathway

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

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

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Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway

Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway