Stattic inhibits RANKL-mediated osteoclastogenesis by suppressing activation of STAT3 and NF-κB pathways

Li, Changhong; Xu, Luo; Jian, Leilei; Yu, Ruiyang; Zhao, Jinxia; Sun, Lin; Du, Guohong; Xiangyuan, Liu

doi:10.1016/j.intimp.2018.03.021

Cited by 53 publications

(39 citation statements)

References 27 publications

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“…For phospho-STAT3 inhibition experiment on Neurocult proliferation cultures, 25,000 cells were allowed to attach and growth as monolayer using a coating of laminin matrix (1:100, Sigma) during 3 days. Then, Stattic an irreversible Stat3 inhibitor (S7947, Sigma, St. Louis, MO, United States) was added to the medium at 0, 1, and 2.5 μM concentration for 72 h as previously described (Li et al, 2018) and then cells were fixed for immunofluorescence analysis.…”

Section: Methodsmentioning

confidence: 99%

Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain

et al. 2019

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Dental pulp stem cells (DPSCs) have the capacity to give rise to cells with neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult genetically unmodified human DPSCs cultured in Neurocult TM (Stem Cell Technologies), a cell culture medium without serum which can be alternatively supplemented for the expansion and/or differentiation of adult neural stem cells (NSCs). Our results show that non-genetically modified human adult DPSCs cultured with Neurocult NS-A proliferation supplement generated neurosphere-like dentospheres expressing the NSC markers Nestin and glial fibrillary acidic protein (GFAP), but also the vascular endothelial cell marker CD31. Remarkably, 1 month after intracranial graft into athymic nude mice, human CD31+/CD146+ and Nestin+ DPSC-derived cells were found tightly associated with both the endothelial and pericyte layers of brain vasculature, forming full blood vessels of human origin which showed an increased laminin staining. These results are the first demonstration that DPSC-derived cells contributed to the generation of neovasculature within brain tissue, and that Neurocult and other related serum-free cell culture media may constitute a fast and efficient way to obtain endothelial cells from human DPSCs.

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Section: Methodsmentioning

confidence: 99%

Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain

et al. 2019

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“…Although, studies show that STAT2 could be implicated in bone homeostasis through STAT1; while STAT4 and STAT6 are involved in inflammatory arthritis [70]. It has been shown that STAT 3 inhibition induced a reduction of RANKL levels and decrease bone resorption through a decline of osteoclast activity mediated by RANKL in several experimental animal models of inflammatory arthritis [71,72]; accordingly, in vitro studies showed that the STAT 3 inhibition induced a reduction of RANKL-mediated osteoclast differentiation from monocytes in mice and human [73,74]. Among all the STATs proteins, STAT1 and STAT3 play a more important role in bone maintenance.…”

Section: Implication Of Jak/stat In Bone Metabolismmentioning

confidence: 99%

JAK/STAT pathway and molecular mechanism in bone remodeling

et al. 2020

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JAK/STAT signaling pathway is involved in many diseases, including autoimmune diseases, which are characterized by a close interconnection between immune and bone system. JAK/STAT pathway is involved in bone homeostasis and plays an important role in proliferation and differentiation of some cell types, including osteoblasts and osteoclasts. Different molecules, such as cytokines, hormones, and growth factors are responsible for the activation of the JAK/STAT pathway, which leads, at the nuclear level, to start DNA transcription of target genes. Bone cells and remodeling process are often influenced by many cytokines, which act as strong stimulators of bone formation and resorption. Our aim, through careful research in literature, has been to provide an overview of the role of the JAK/STAT pathway in bone remodeling and on bone cells, with a focus on cytokines involved in bone turnover through this signal cascade. The JAK/STAT pathway, through the signal cascade activation mediated by the interaction with many cytokines, acts on bone cells and appears to be involved in bone remodeling process. However, many other studies are needed to completely understand the molecular mechanism underlying these bone process.

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“…On the other hand, Virginia J. Savinet et al [35] reported that CLCF1 is a potential "circulating factor" in the human renal disease focal segmental glomerulosclerosis (FSGS), and it acts by initiating the JAK/STAT signaling pathway in glomerular podocytes. Besides, the JAK2/STAT3 pathway has been associated with a vital role in the origination and evolution of osteoporosis [36,37]. In particular, a recent study demonstrated that the JAK2/STAT3…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Cardiotrophin-Like Cytokine 1(CLCF1) Inhibits Osteoblastic Differentiation by Regulating RANKL/ OPG Pathway

Chen¹,

Xu²,

Ye³

et al. 2020

Preprint

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BackgroundCardiotrophin-like cytokine factor 1 (CLCF1) is a member of the IL (interleukin)-6-type cytokine. Although its immunomodulatory functions are well defined, data on the physiological and pathological functions of the CLCF1 in bone metabolism remains scant. Here, we interrogated the functions and mechanisms of CLCF1 in osteoblast differentiation.MethodsA total of 109 patients with postmenopausal osteoporosis (PMOP) and 94 control group participants were included in this study. Quantitative reverse transcription PCR (RT-qPCR) and Western blot techniques were used to profile the expression of the CLCF1, nuclear factor-kB ligand and its decoy receptor osteoprotegerin (RANKL/OPG), as well as the janus activated kinase (JAK2)/transcription3 (STAT3) pathway. To elucidate the effect of CLCF1 on bone metabolism, we established CLCF1 gene-knockout Raji cell lines and Raji-MG-63 co-culture system, and interrogated the osteoblast differentiation by measuring the activity of ALP and the level of Alizarin-Red S staining.ResultsOur data demonstrated that the expression of CLCF1 was highly downregulated in PMOP compared with the control group. Moreover, the level of CLCF1 was proportional to the bone mineral density (BMD) in the postmenopausal osteoporosis. Furthermore, the deletion of CLCF1 gene inhibits osteoblast differentiation by regulating the RANKL/OPG system.ConclusionOur findings unravel the previously unidentified roles of CLCF1 in the bone-immune crosstalk, as well as potential therapeutic strategies for postmenopausal osteoporosis.

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Stattic inhibits RANKL-mediated osteoclastogenesis by suppressing activation of STAT3 and NF-κB pathways

Cited by 53 publications

References 27 publications

Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain

Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain

JAK/STAT pathway and molecular mechanism in bone remodeling

Downregulation of Cardiotrophin-Like Cytokine 1(CLCF1) Inhibits Osteoblastic Differentiation by Regulating RANKL/ OPG Pathway

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