Ameloblastin promotes bone growth by enhancing proliferation of progenitor cells and by stimulating immunoregulators

Tamburstuen, Margareth V.; Reppe, Sjur; Spahr, Axel; Sabetrasekh, Roya; Kvalheim, Gunnar; Slaby, Ivan; Syversen, Unni; Lyngstadaas, Ståle Petter; Reseland, Janne Elin

doi:10.1111/j.1600-0722.2010.00760.x

Cited by 30 publications

(39 citation statements)

References 55 publications

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“…However, a previous study showed that EMD stimulated proliferation of human periodontal cells, as well as epithelial cell rests of Malazzez, gingival fibroblasts, and osteoblasts 9 . In addition, recombinant ameloblastin has been shown to stimulate the proliferation of human mesenchymal stem cells and osteoblasts 26 . Together, these findings indicate that the effect of ameloblastin on cell proliferation varies according to cell type.…”

Section: Discussionmentioning

confidence: 95%

Novel biological activity of ameloblastin in enamel matrix derivative

et al. 2015

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Objective Enamel matrix derivative (EMD) is used clinically to promote periodontal tissue regeneration. However, the effects of EMD on gingival epithelial cells during regeneration of periodontal tissues are unclear. In this in vitro study, we purified ameloblastin from EMD and investigated its biological effects on epithelial cells.Material and Methods Bioactive fractions were purified from EMD by reversed-phase high-performance liquid chromatography using hydrophobic support with a C18 column. The mouse gingival epithelial cell line GE-1 and human oral squamous cell carcinoma line SCC-25 were treated with purified EMD fraction, and cell survival was assessed with a WST-1 assay. To identify the proteins in bioactive fractions of EMD, we used proteome analysis with two-dimensional gel electrophoresis followed by identification with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.Results Purified fractions from EMD suppressed proliferation of GE-1 and SCC-25. LC-MS/MS revealed that ameloblastin in EMD is the component responsible for inhibiting epithelial cell proliferation. The inhibitory effect of ameloblastin on the proliferation of GE-1 and SCC-25 was confirmed using recombinant protein.Conclusion The inhibitory effects of EMD on epithelial cell proliferation are caused by the biological activities of ameloblastin, which suggests that ameloblastin is involved in regulating epithelial downgrowth in periodontal tissues.

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Section: Discussionmentioning

confidence: 95%

Novel biological activity of ameloblastin in enamel matrix derivative

et al. 2015

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“…Consistently and in line with previous studies [40], aging was associated with decreased gene expression of EMPs in jaw bones. Recently, increased expression of AMBN was also shown to be associated with mechanical bone stimulation [41] and healing [42]. Interestingly, MSX2, a regulator of bone homeostasis [33] represses AMELX transcription by targeting the AMELX promoter [43] and both AMELX and AMBN inhibit Msx2 expression [44], [45].…”

Section: Discussionmentioning

confidence: 99%

“…Haze, 2009 [8]; Tamburstuen, 2011 [10], 2. Zeichner-David, 2006 [57]; Fukae, 2006 [58]; Matsuzawa, 2009 [59]; Tambursten, 2010 [42]; Kakegawa, 2010 [60]; Zhang, 2011 [54]; Kitagawa, 2011 [53]; Kunimatsu, 2011 [61]; Izumikawa, 2012 [62]; Amin, 2013 [63], 3. Spahr, 2006 [36]; Haze, 2009 [8]; Iizuka, 2011 [18]; Tamburstuen, 2011 [10]; Atsawasuwan, 2013 [40], 4.…”

Section: Discussionmentioning

confidence: 99%

Tracking Endogenous Amelogenin and Ameloblastin In Vivo

et al. 2014

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Research on enamel matrix proteins (EMPs) is centered on understanding their role in enamel biomineralization and their bioactivity for tissue engineering. While therapeutic application of EMPs has been widely documented, their expression and biological function in non-enamel tissues is unclear. Our first aim was to screen for amelogenin (AMELX) and ameloblastin (AMBN) gene expression in mandibular bones and soft tissues isolated from adult mice (15 weeks old). Using RT-PCR, we showed mRNA expression of AMELX and AMBN in mandibular alveolar and basal bones and, at low levels, in several soft tissues; eyes and ovaries were RNA-positive for AMELX and eyes, tongues and testicles for AMBN. Moreover, in mandibular tissues AMELX and AMBN mRNA levels varied according to two parameters: 1) ontogenic stage (decreasing with age), and 2) tissue-type (e.g. higher level in dental epithelial cells and alveolar bone when compared to basal bone and dental mesenchymal cells in 1 week old mice). In situ hybridization and immunohistodetection were performed in mandibular tissues using AMELX KO mice as controls. We identified AMELX-producing (RNA-positive) cells lining the adjacent alveolar bone and AMBN and AMELX proteins in the microenvironment surrounding EMPs-producing cells. Western blotting of proteins extracted by non-dissociative means revealed that AMELX and AMBN are not exclusive to mineralized matrix; they are present to some degree in a solubilized state in mandibular bone and presumably have some capacity to diffuse. Our data support the notion that AMELX and AMBN may function as growth factor-like molecules solubilized in the aqueous microenvironment. In jaws, they might play some role in bone physiology through autocrine/paracrine pathways, particularly during development and stress-induced remodeling.

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“…The following inferred gene AMBN (ENSP00000313809) encodes a functional extracellular matrix protein in the dentin microenvironment, which has been confirmed to participate in the regeneration of the tooth root [39,40]. As for its functional roles during bone regeneration, it has been confirmed that such gene directly regulates the remodeling and repair of osseous tissues [41,42], verifying its specific co-regenerative biological functions. The last gene turns out to be PTCH1 (ENSP00000332353).…”

Section: Co-regeneration Genes For Bone and Dentinementioning

confidence: 94%

Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues

Lei

Pan

Zhang

et al. 2017

Genes

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Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

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Ameloblastin promotes bone growth by enhancing proliferation of progenitor cells and by stimulating immunoregulators

Cited by 30 publications

References 55 publications

Novel biological activity of ameloblastin in enamel matrix derivative

Novel biological activity of ameloblastin in enamel matrix derivative

Tracking Endogenous Amelogenin and Ameloblastin In Vivo

Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues

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