Bone-protective Functions of Netrin 1 Protein

Maruyama, Kei; Kawasaki, Tadahiro; Hamaguchi, Masahide; Hashimoto, Motomu; Furu, Moritoshi; Ito, Hiromu; Fujii, Tomoyuki; Takemura, Nobuyuki; Karuppuchamy, Thangaraj; Kondo, Takeshi; Kawasaki, Takumi; Fukasaka, Masahiro; Misawa, Takuma; Saitoh, Tatsuya; Suzuki, Yutaka; Martino, Mikaël M.; Kumagai, Yutaro; Akira, Shizuo

doi:10.1074/jbc.m116.738518

Cited by 28 publications

(36 citation statements)

References 53 publications

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“…Netrin-1 is a neuroimmune guidance cue. It can inhibit the migration of macrophages, which means that it is an inflammatory factor3536. This can explain the reduced transwell rate of RAW 264.7 cell by polyethylene debris in our study.…”

Section: Discussionmentioning

confidence: 50%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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Previous studies have shown that Low intensity pulsed ultrasound(LIPUS) prevents polyethylene-debris-induced periprosthetic loosening in vivo, but the details of the mechanism by which it does so remain unclear. In this article, we used polyethylene debris induced RAW 264.7 cells as the in vitro model, and tested the effect of LIPUS on this model. Changes in the level of inflammatory cytokines, cell proliferation, and apoptosis were assessed. Gene overexpression and siRNA technique were applied, and the levels of expression of FBXL2, TRAF6, ERK, and related inflammatory cytokines were also measured. Results indicated that FBXL2-mediated TRAF6 ubiquitination and degradation also plays an important role in aseptic periprosthetic loosening process, and LIPUS prevents such loosening by strengthening this pathway.

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Section: Discussionmentioning

confidence: 50%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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“…In addition to the regulation of immune cell migration, Netrin‐1 was shown to regulate the inflammatory response of macrophages through suppression of COX‐2–mediated PGE2 production and also promote macrophage reprogramming to induce inflammation resolution . Furthermore, Netrin‐1 binding with its receptor Unc5b takes part in osteoclast biology and thus suggested as a therapeutic target for inflammatory bone destructive diseases . In this study, Netrin‐1 and its receptor Unc5b were detected in all samples.…”

Section: Discussionmentioning

confidence: 56%

“…In addition to the anti‐inflammatory properties, Netrin‐1/Unc5b interaction takes apart in bone destructive diseases impacting through osteoclast fusion. Blockade of Netrin‐1/Unc5b axis has been shown to prevent bone destruction .…”

Section: Introductionmentioning

confidence: 99%

Netrin‐1 and its receptor Unc5b as markers of periodontal disease

Günpınar

Meraci

Dündar

2019

J of Periodontal Research

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Objectives The aim of this present study was to evaluate the levels of Netrin‐1 and Unc5b in periodontal health and disease. Background Netrin‐1, acting via its receptor UNC5b, regulates the inflammatory response and takes apart in bone destructive diseases. Methods Samples of gingival crevicular fluid (GCF), whole saliva, and serum were taken from systemically healthy, nonsmoking 20 periodontitis , 20 gingivitis patients, and 20 periodontally healthy subjects at baseline and 4 weeks after nonsurgical periodontal treatment (NSPT). Whole‐mouth and site‐specific clinical periodontal parameters were recorded. Netrin‐1 and Unc5b levels were measured by enzyme‐linked immunosorbent assay. Data were analyzed by nonparametric tests. Results Total amount of Netrin‐1 in GCF was significantly higher in periodontitis than the others, and the levels were significantly reduced after NSPT. Salivary and serum concentrations of Netrin‐1 were significantly different among the study groups (P = .000), and NSPT significantly increased the concentration levels of both salivary and serum Netrin‐1 (P < .05). Healthy subjects had significantly lower GCF (P = .001) and conversely, higher salivary and serum levels of Unc5b than the other groups (P = .002). The GCF levels of Unc5b were significantly reduced (P < .01), and conversely, serum concentrations were significantly increased after NSPT (P < .05). GCF Netrin‐1 and Unc5b total amounts were positively correlated with clinical parameters (P < .01 and P < .05) whereas salivary Netrin‐1 and Unc5b concentrations were negatively correlated with clinical parameters (P < .01 and P < .05). Conclusions The results of this study indicate that Netrin‐1 and its receptor Unc5b may have essential roles in periodontal inflammation and those can be assumed as useful therapeutic agent to control inflammation and periodontal breakdown.

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“…Mediero et al demonstrated that Ntn1, which is produced by osteoclasts enhanced osteoclast differentiation by an autocrine/paracrine manner and Ntn1 deficient mice have markedly diminished osteoclasts, as well as increased cortical and trabecular bone density and volume compared to wildtype mice, suggesting that Ntn1 is a negative regulator in bone metabolism (11). In contrast, Maruyama et al reported that Ntn1 suppresses osteoclast multinucleation, but not osteoclast differentiation and protected the mice against autoimmune bone destruction in vivo, indicating that Ntn1 is a positive regulator in bone metabolism (12). These researchers reported that Ntn1 does not affect osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 94%

“…Among these netrins, netrin-1 (Ntn1) has involved in cytoskeleton reorganization and in epithelial cell adhesion and migration in lung, mammary gland, and pancreas (8-10). Recent studies showed that Ntn1 plays a crucial role in osteoclast differentiation (11,12). As the function of osteoclasts is regulated by Ntn1, the question whether Ntn1 affects cellular function in osteoblasts has been raised.…”

mentioning

confidence: 99%

Functional Roles of Netrin-1 in Osteoblast Differentiation

Sato

Kokabu

Enoki

et al. 2017

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Bone tissue is constantly being remodeled to maintain its homeostasis by osteoblasts and the resorption by osteoclasts (1). The function of bone tissue is regulated by several factors which other organs produce to communicate with bones. Indeed, the vessels and nerves inside bone are essential for bone development and remodeling (2, 3). Previous studies have demonstrated that neural and vascular regulation factors, such as semaphorins and netrins, orchestrate bone metabolism. We have demonstrated that semaphorin 3A, which is a diffusible axonal chemorepellent that has an important role in axon guidance, regulates bone remodeling indirectly by modulating sensory nerve development and also found that it enhances the elongation of dendrite in osteocytes (4, 5). Semaphorin 3A exerts an osteoprotective effect by both suppressing bone resorption and increasing bone formation (6).Mammalian netrins including the secreted proteins (netrin-1, netrin-3, netrin-4 and netrin-5) and membrane-bound proteins (netrin-G1 and netrin-G2) are involved in the regulation of both axon guidance and angiogenesis (7). The netrin system comprises of seven receptors including neogenin (Neo1), deleted in colorectal carcinoma (DCC), Unc5A, Unc5B, Unc5C, Unc5D, adenosine 2b (A2b), and Down syndrome cell adhesion molecule (DSCAM) (7). Among these netrins, netrin-1 (Ntn1) has involved in cytoskeleton reorganization and in epithelial cell adhesion and migration in lung, mammary gland, and pancreas (8-10). Recent studies showed that Ntn1 plays a crucial role in osteoclast differentiation (11,12). As the function of osteoclasts is regulated by Ntn1, the question whether Ntn1 affects cellular function in osteoblasts has been raised. However, little is known about the role of Ntn1 in osteoblasts. In this study, we explore whether Ntn1 affects the function of osteoblasts. Materials and ΜethodsCell culture, reagents and transfection. The mouse pre-osteoblastic cell line MC3T3-E1 cells which were kindly provided from Dr. Toru Ogasawara (Department of Oral and Maxillofacial Surgery, The University of Tokyo, Japan) were maintained in the medium, 321

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Bone-protective Functions of Netrin 1 Protein

Cited by 28 publications

References 53 publications

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Netrin‐1 and its receptor Unc5b as markers of periodontal disease

Functional Roles of Netrin-1 in Osteoblast Differentiation

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