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  • 1
    In: Orthodontics & Craniofacial Research, Wiley, Vol. 26, No. 4 ( 2023-11), p. 632-641
    Abstract: Pathological dental root resorption and alveolar bone loss are often detected only after irreversible damage. Biomarkers in the gingival crevicular fluid or saliva could provide a means for early detection; however, such biomarkers have proven elusive. We hypothesize that a multiomic approach might yield reliable diagnostic signatures for root resorption and alveolar bone loss. Previously, we showed that extracellular vesicles (EVs) from osteoclasts and odontoclasts differ in their protein composition. In this study, we investigated the metabolome of EVs from osteoclasts, odontoclasts and clasts (non‐resorbing clastic cells). Materials and Methods Mouse haematopoietic precursors were cultured on dentine, bone or plastic, in the presence of recombinant RANKL and CSF‐1 to trigger differentiation along the clastic line. On Day 7, the cells were fixed and the differentiation state and resorptive status of the clastic cells were confirmed. EVs were isolated from the conditioned media on Day 7 and characterized by nanoparticle tracking and electron microscopy to ensure quality. Global metabolomic profiling was performed using a Thermo Q‐Exactive Orbitrap mass spectrometer with a Dionex UHPLC and autosampler. Results We identified 978 metabolites in clastic EVs. Of those, 79 are potential biomarkers with Variable Interdependent Parameters scores of 2 or greater. Known metabolites cytidine, isocytosine, thymine, succinate and citrulline were found at statistically higher levels in EVs from odontoclasts compared with osteoclasts. Conclusion We conclude that numerous metabolites found in odontoclast EVs differ from those in osteoclast EVs, and thus represent potential biomarkers for root resorption and periodontal tissue destruction.
    Type of Medium: Online Resource
    ISSN: 1601-6335 , 1601-6343
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2098407-8
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2001
    In:  American Journal of Orthodontics and Dentofacial Orthopedics Vol. 120, No. 5 ( 2001-11), p. 477-489
    In: American Journal of Orthodontics and Dentofacial Orthopedics, Elsevier BV, Vol. 120, No. 5 ( 2001-11), p. 477-489
    Type of Medium: Online Resource
    ISSN: 0889-5406
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 2021368-2
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  • 3
    Online Resource
    Online Resource
    Informa UK Limited ; 2012
    In:  Journal of Orthodontics Vol. 39, No. 3 ( 2012-09), p. 170-175
    In: Journal of Orthodontics, Informa UK Limited, Vol. 39, No. 3 ( 2012-09), p. 170-175
    Type of Medium: Online Resource
    ISSN: 1465-3125 , 1465-3133
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2012
    detail.hit.zdb_id: 1466695-9
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  • 4
    Online Resource
    Online Resource
    The Angle Orthodontist (EH Angle Education & Research Foundation) ; 2011
    In:  The Angle Orthodontist Vol. 81, No. 6 ( 2011-11), p. 1083-1089
    In: The Angle Orthodontist, The Angle Orthodontist (EH Angle Education & Research Foundation), Vol. 81, No. 6 ( 2011-11), p. 1083-1089
    Type of Medium: Online Resource
    ISSN: 0003-3219 , 1945-7103
    RVK:
    Language: English
    Publisher: The Angle Orthodontist (EH Angle Education & Research Foundation)
    Publication Date: 2011
    detail.hit.zdb_id: 2026352-1
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  • 5
    Online Resource
    Online Resource
    MRE Press ; 2018
    In:  Journal of Clinical Pediatric Dentistry Vol. 42, No. 2 ( 2018-01-01), p. 95-102
    In: Journal of Clinical Pediatric Dentistry, MRE Press, Vol. 42, No. 2 ( 2018-01-01), p. 95-102
    Abstract: Objectives: Due to the low prevalence of localized aggressive periodontitis (LAP), clinical characteristics of LAP in primary dentition are derived from a few case reports/series in the literature. The goal of this study was to determine common clinical characteristics such as bone and root resorption patterns, in a series of cases with LAP in primary dentition. We hypothesize these cases present aggressive periodontal bone destruction starting mostly around first primary molars and atypical root resorption patterns. Study Design: We have evaluated 33 LAP cases in primary dentition for pattern of bone destruction, root resorption and early exfoliation. Results: Cases evaluated were aged 5–12 (mean=8.7 years). Thirty cases presented more severe bone loss on first than second molars, with relatively fast progression to second molars, altered pattern of root resorption, mostly external (n=16) and early exfoliation of primary teeth due to periodontal bone loss, rather than physiologic root resorption (n=11). Conclusions: This study showed common clinical characteristics found in LAP in primary molars, including possible initiation on first primary molars and abnormal root resorption patterns. These characteristics are important to be early identified and treated in order to prevent possible progression into the permanent dentition.
    Type of Medium: Online Resource
    ISSN: 1053-4628 , 1557-5268
    Language: English
    Publisher: MRE Press
    Publication Date: 2018
    detail.hit.zdb_id: 2109214-X
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-04-28)
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-04-28)
    Abstract: The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H + -ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the “handle region peptide” from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 21, No. 1 ( 2019-12-25), p. 158-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 1 ( 2019-12-25), p. 158-
    Abstract: Extracellular vesicles (EVs) are shed by all eukaryotic cells and have emerged as important intercellular regulators. EVs released by osteoclasts were recently identified as important coupling factors in bone remodeling. They are shed as osteoclasts resorb bone and stimulate osteoblasts to form bone to replace the bone resorbed. We reported the proteomic content of osteoclast EVs with data from two-dimensional, high resolution liquid chromatography/mass spectrometry. In this article, we examine in detail the actin and actin-associated proteins found in osteoclast EVs. Like EVs from other cell types, actin and various actin-associated proteins were abundant. These include components of the polymerization machinery, myosin mechanoenzymes, proteins that stabilize or depolymerize microfilaments, and actin-associated proteins that are involved in regulating integrins. The selective incorporation of actin-associated proteins into osteoclast EVs suggests that they have roles in the formation of EVs and/or the regulatory signaling functions of the EVs. Regulating integrins so that they bind extracellular matrix tightly, in order to attach EVs to the extracellular matrix at specific locations in organs and tissues, is one potential active role for actin-associated proteins in EVs.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-11-01)
    Abstract: Enoxacin and its bone-seeking bisphosphonate derivative, bis-enoxacin, have recently captured attention as potential therapeutic agents for the treatment of cancer and bone disease. No differences in growth or survival of 4T1 murine breast cancer cells were detected at a concentration of 50 µM of enoxacin or bis-enoxacin. Growth was perturbed at higher concentrations. Both 50 µM enoxacin and bis-enoxacin stimulated increases in the number of GW/Processing bodies, but there were minimal changes in microRNA levels. Extracellular vesicles (EVs) released from 4T1 cells treated with 50 µM enoxacin or 50 µM bis-enoxacin stimulated proliferation of RAW 264.7 cells, and both significantly inhibited osteoclastogenesis in calcitriol-stimulated mouse marrow. EVs from 4T1 cells treated with enoxacin and bis-enoxacin displayed small reductions in the amount of microRNA (miR)-146a-5p and let-7b-5p. In marked contrast, miR-214-3p, which has been shown to regulate bone remodeling, was increased 22-fold and 30-fold respectively. We conclude that enoxacin and bis-enoxacin trigger the release of EVs from 4T1 cancer cells that inhibit osteoclastogenesis.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2615211-3
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  • 9
    Online Resource
    Online Resource
    The Angle Orthodontist (EH Angle Education & Research Foundation) ; 2012
    In:  The Angle Orthodontist Vol. 82, No. 3 ( 2012-05), p. 546-551
    In: The Angle Orthodontist, The Angle Orthodontist (EH Angle Education & Research Foundation), Vol. 82, No. 3 ( 2012-05), p. 546-551
    Type of Medium: Online Resource
    ISSN: 0003-3219 , 1945-7103
    RVK:
    Language: English
    Publisher: The Angle Orthodontist (EH Angle Education & Research Foundation)
    Publication Date: 2012
    detail.hit.zdb_id: 2026352-1
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  • 10
    Online Resource
    Online Resource
    The Angle Orthodontist (EH Angle Education & Research Foundation) ; 2014
    In:  The Angle Orthodontist Vol. 84, No. 1 ( 2014-01-01), p. 120-126
    In: The Angle Orthodontist, The Angle Orthodontist (EH Angle Education & Research Foundation), Vol. 84, No. 1 ( 2014-01-01), p. 120-126
    Abstract: To investigate differences in the gingival crevicular fluid (GCF) composition between adolescent and adult patients undergoing orthodontic treatment with fixed appliances. Materials and Methods: Ten adolescents (14.4 ± 1.43) and 10 adults (28.5 ± 7.83) with Class I malocclusions and minor upper incisor crowding were allocated to two different age groups. Brackets were bonded only in the upper arch over the 20-week period of the experiment. Samples of GCF were collected from the labial sides of the upper incisors (experimental sites) and lower incisors (control sites) of each subject at five time points. Aliquots from diluted GCF were screened for the presence of receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), interleukin-1 (IL-1), interleukin-1 receptor antagonist (IL-1RA), and metalloproteinase-9 (MMP-9) using a microarray technique. The values were statistically analyzed. Results: In adults, the ratio of IL-1 to IL-1RA decreased significantly (P  =  .033) in experimental sites 3 weeks after appliance placement and first archwire activation. In adolescents, the ratio of RANKL to OPG peaked 6 weeks after the insertion of the first rectangular archwire. This ratio peak found in adolescents was a consequence of a decrease in the mean concentration of OPG. No significant changes over time were observed in the concentration of MMP-9. Conclusion: This study demonstrates age trends in the GCF levels of IL-1, IL-1RA, RANKL, and OPG that may be used to track differences in tissue response between adults and adolescents undergoing orthodontic treatment.
    Type of Medium: Online Resource
    ISSN: 0003-3219 , 1945-7103
    RVK:
    Language: English
    Publisher: The Angle Orthodontist (EH Angle Education & Research Foundation)
    Publication Date: 2014
    detail.hit.zdb_id: 2026352-1
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