Tumor necrosis factor alpha suppresses osteogenic differentiation of MSCs by inhibiting semaphorin 3B via Wnt/β-catenin signaling in estrogen-deficiency induced osteoporosis

Sang, Chenglin; Zhang, Yongxian; Chen, Fangjing; Huang, Ping; Qi, Jin; Wang, Pingshan; Zhou, Qi; Kang, Hui; Cao, Xuecheng; Guo, Lei

doi:10.1016/j.bone.2015.12.012

Cited by 49 publications

(57 citation statements)

References 37 publications

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“…However, the specific mechanisms by which SMURF1 negatively regulate osteogenesis remain unclear. The present study demonstrated that TNFα can significantly suppress MSCs osteogenesis, which is consistent with many previous reports . Then, results showed that TNFα halted osteogenesis by downregulating SMAD1 protein and subsequently blocking the activity of BMP‐SMAD1 pathway, which is a key positive regulator of osteogenesis, and the crosstalk between BMP signaling and TNFα signaling in regulation of bone formation has been confirmed by many other researches .…”

Section: Discussionsupporting

confidence: 92%

“…Tumor necrosis factor‐alpha has been documented to regulate bone remodeling by suppressing osteogenesis and activating osteoclastogenesis . Quite a few signaling pathways are involved in mediating the effects of TNFα on osteogenesis as reported . Among them, SMURF1 seems particularly notable because SMURF1 itself is a well‐known negative regulator of bone formation.…”

Section: Discussionmentioning

confidence: 99%

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Melatonin reversed tumor necrosis factor‐alpha‐inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein

Lian

Gao

et al. 2016

Journal of Pineal Research

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Tumor necrosis factor-alpha (TNFα) plays a pivotal role in inflammation-related osteoporosis through the promotion of bone resorption and suppression of bone formation. Numerous drugs have been produced to treat osteoporosis by inhibiting bone resorption, but they offer few benefits to bone formation, which is what is needed by patients with severe bone loss. Melatonin, which can exert both anti-inflammatory and pro-osteogenic effects, shows promise in overcoming TNFα-inhibited osteogenesis and deserves further research. This study demonstrated that melatonin rescued TNFα-inhibited osteogenesis of human mesenchymal stem cells and that the interactions between SMURF1 and SMAD1 mediated the crosstalk between melatonin signaling and TNFα signaling. Additionally, melatonin treatment was found to downregulate TNFα-induced SMURF1 expression and then decrease SMURF1-mediated ubiquitination and degradation of SMAD1 protein, leading to steady bone morphogenetic protein-SMAD1 signaling activity and restoration of TNFα-impaired osteogenesis. Thus, melatonin has prospects for treating osteoporosis caused by inflammatory factors due to its multifaceted functions on regulation of bone formation, bone resorption, and inflammation. Further studies will focus on unveiling the specific mechanisms by which melatonin downregulates SMURF1 expression and confirming the clinical therapeutic value of melatonin in the prevention and therapy of bone loss associated with inflammation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Melatonin reversed tumor necrosis factor‐alpha‐inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein

Lian

Gao

et al. 2016

Journal of Pineal Research

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“…For example, TNF/TNFR1 signaling promoted osteoclastogenesis by JNK signaling-induced expression of semaphorin 3D [24]. Another study showed that TNF/TNFR1 signaling suppressed bone formation in estrogen deficiency-induced osteoporosis by inhibiting semaphorin 3B via Wnt/β-catenin signaling [25]. Gerstenfeld et al [26] suggested that TNF/ .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-218 Negatively Regulates Osteoclastogenic Differentiation by Repressing the Nuclear Factor-κB Signaling Pathway and Targeting Tumor Necrosis Factor Receptor 1

Wang

Yang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Postmenopausal osteoporosis is a common disease associated with estrogen deficiency leading to bone loss and bone tissue changes. The resultant bone fragility and increased risk of fracture has serious adverse effects on health and quality of life of the elderly, making it an important health issue. MicroRNA-218 (miR-218) is closely related to the development of osteoporosis. In this study, we investigated the regulatory mechanisms of miR-218 in osteoclastogenesis. Methods: We investigated miR-218 levels on differentiation of RAW 264.7 cells into osteoclasts compared with normal cells. Next, RAW 264.7 cells were transfected with miR-218 mimics or inhibitors to study the role of miR-218 in osteoclastogenic differentiation. Tartrate-resistant acid phosphatase (TRAP) staining was performed to determine osteoclastogenic differentiation. Bioinformatics analysis and luciferase reporter assay were used to identify and validate miR-218 target genes. Results: miR-218 was downregulated following RAW 264.7 cell differentiation into osteoclasts. miR-218 overexpression attenuated osteoclast differentiation, whereas low miR-218 expression promoted it as demonstrated by increased expression of osteoclast-specific genes and TRAP staining. Bioinformatics analysis and the luciferase reporter assay showed that tumor necrosis factor receptor 1 (TNFR1), a cell membrane receptor of TNF (TNF is an activator of nuclear factor-κB [NF-κB]), is a direct target of miR-218. Conclusions: Our findings indicate that miR-218 regulates osteoclastogenic differentiation negatively by repressing NF-κB signaling by targeting TNFR1, suggesting that targeting miR-218 may be a therapeutic approach in postmenopausal osteoporosis.

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“…Recent studies have indicated that semaphorin plays an important role in nervous system development, immune responses, angiogenesis and tumor development [1,15]. The semaphorin gene encodes three types of proteins including transmembrane proteins, membrane proteins and secreted proteins.…”

Section: The Semaphorin Family and Sema3bmentioning

confidence: 99%

“…The semaphorins area large protein superfamily that is mainly composed of membrane proteins or secreted proteins [1,2]. Semaphorin 3B (SEMA3B), a tumor suppressor gene, is a member of the semaphorin family and is located on 3p21.3 [3].…”

Section: Introductionmentioning

confidence: 99%

Semaphorin 3B Gene Suppresses Tumor Growth Through the p53 Signaling Pathway and Neuropilin Receptors

Ma¹

2017

AJCEM

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Abstract:The semaphorin family has been demonstrated to possess tumor suppressor activity; semaphorin 3B (SEMA3B) is differentially expressed in several types of tumors, and has been identified as a tumor suppressor gene. SEMA3B is shown to be a target gene of p53, and it suppresses tumor growth through the p53 signaling pathway. The mechanisms underlying tumor suppression by SEMA3B include neuropilin receptors (NRP1 and NRP2), which reduce the action of vascular endothelial growth factor (VEGF), thus, inhibiting tumor angiogenesis. Deficiency or down-regulation of SEMA3B expression can be found in a variety of malignant tumors including lung cancer, ovarian cancer, nervous system tumors, and hepatobiliary tumors, and this suppression involves methylation, loss of heterozygosity (LOH) and enzyme cleavage. This review summarizes recent research approaches on the tumor suppression effects and mechanisms of SEMA3B.

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Tumor necrosis factor alpha suppresses osteogenic differentiation of MSCs by inhibiting semaphorin 3B via Wnt/β-catenin signaling in estrogen-deficiency induced osteoporosis

Cited by 49 publications

References 37 publications

Melatonin reversed tumor necrosis factor‐alpha‐inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein

Melatonin reversed tumor necrosis factor‐alpha‐inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein

MicroRNA-218 Negatively Regulates Osteoclastogenic Differentiation by Repressing the Nuclear Factor-κB Signaling Pathway and Targeting Tumor Necrosis Factor Receptor 1

Semaphorin 3B Gene Suppresses Tumor Growth Through the p53 Signaling Pathway and Neuropilin Receptors

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