菸醯胺磷酸核糖基轉移酶 (Nicotinamide phosphoribosyltransferase，NAMPT)，又稱為Visfatin或是PBEF (Pre-B-cell colony-enhancing factor)是一個主要由內臟脂肪細胞分泌，分子量約為52kDa且由491個氨基酸所組成的蛋白質。目前已知NAMPT會藉由： 1.調控單核細胞來影響發炎因子的分泌、 2.調控T細胞的活化、 3.調控CD4+monocyte與CD19+B細胞的趨化、 4.抑制嗜中性球的凋亡來延長發炎反應的時間等方式來調控發炎與免疫反應。
由先前的文獻得知牙齦溝液與血清中NAMPT的濃度會隨著牙周疾病的嚴重程度增加而提高。NAMPT也因此被認為可當作牙周組織發炎的指標之一。然而植體周圍炎目前對於牙科來說是個棘手的發炎疾病，所以我們想要探討在牙周健康、慢性牙周炎與植體周圍炎的族群中NAMPT表現差異及其臨床意義。
經由牙周手術分別從牙周健康、慢性牙周炎與植體周圍炎的患者取得軟組織檢體。由Human inflammatory cytokines and receptors PCR array發現NAMPT在慢性牙周炎與植體周圍炎的表現都是偏高的，於是進一步使用real-time PCR分析NAMPT基因在三組之間有無差異。經過Kruskal-Wallis test分析，三組之間沒有顯著差異。
使用免疫組織化學染色(IHC)分析各組檢體中NAMPT蛋白質表現差異。免疫組織化學染色的結果顯示NAMPT在慢性牙周炎與植體周圍炎的檢體有顯著較高的表現。使用酵素連結免疫吸附法(ELISA)分析各組檢體中NAMPT蛋白質的表現，結果顯示NAMPT在牙周炎與植體周圍的表現都比牙周健康的檢體來得高的。
使用細胞培養的實驗評估不同細胞株(HUVEC, DOK, THP-1)加入鈦金屬顆粒後NAMPT的基因表現。結果顯示加入鈦金屬顆粒後NAMPT表現會增加但沒有達到統計上的差異，此外，三株細胞中NAMPT的表現在THP-1是三者中顯著較高的。
未來可再搜集更多檢體利用酵素連結免疫吸附分析法或是西方墨點法等方式證實NAMPT蛋白質在牙周炎與植體周圍炎的表現，並期望可將結果應用在植體周圍炎的治療。

Nicotinamide phosphoribosyltransferase (NAMPT), also known as Visfatin or PBEF (Pre-B-cell colony-enhancing factor), is a 52 kDa protein consisted of 491 amino acid residues and primarily produced by visceral fat cells. NAMPT could regulate immune reaction and inflammation through the following mechanisms : 1. Reciprocally regulates monocytes’ inflammatory mediators secretion (IL-6, IL-1β, TNF-α); 2. T-cell activation; 3. Chemotaxis of CD4+ monocyte and CD19+ B-cell; 4. Inhibit neutrophils apoptosis to prolong the persistence of inflammation.
In the previous studies, gingival crevicular fluid and serum NAMPT concentrations were found to elevate with severity of periodontal disease and NAMPT could be considered as an inflammatory marker. Peri-implantitis is a problematic peri-implant inflammatory disease in modern dentistry. So we aimed to evaluate the NAMPT expression differences between periodontally healthy, chronic periodontitis and peri-implantitis individuals.
Soft tissue specimens were obtained during periodontal surgeries from periodontally healthy, chronic periodontitis and peri-implantitits subjects. Human inflammatory cytokines and receptors PCR array was utilized, and NAMPT expression was upregulated in chronic periodontitis and peri-implantitis lesions. Real-time PCR was performed to evaluate NAMPT expression among all three groups, and results were analyzed using Kruskal-Wallis test. No significant difference was found between all three groups.
Immunohistochemistry (IHC) was utilized to confirm NAMPT expression levels. IHC results showed significant more NAMPT-containing cells in chronic periodontitis and peri-implantitis compared with healthy groups. Enzyme-Linked ImmunoSorbent Assay (ELISA) was utilized NAMPT protein expression in tissue specimens. The ELISA result showed higher NAMPT protein expression in chronic periodontitis and peri-implantitis compared with periodontally healthy sample.
An in vitro study was design to evaluate whether titanium particles have impact on NAMPT mRNA expression in three cell lines (HUVEC, DOK, THP-1). The result showed an increasing tendency of NAMPT expression after titanium treatment and THP-1 cells expressed significantly higher NAMPT than HUVEC and DOK cells.
In the future, the NAMPT protein levels in chronic periodontitis and peri-implantitis lesions could be confirmed in more samples by enzyme-linked immunosorbent assay (ELISA) or western blot. The result could be applied in treatment of peri-implantitis in the future.

(2013). Academy Report: Peri-Implant Mucositis and Peri-Implantitis: A Current Understanding of Their Diagnoses and Clinical Implications. Journal of Periodontology 84, 436-443.
Auwerx, J., Staels, B., Van Vaeck, F., and Ceuppens, J.L. (1992). Changes in IgG Fc receptor expression induced by phorbol 12-myristate 13-acetate treatment of THP-1 monocytic leukemia cells. Leukemia research 16, 317-327.
Baelum, V., and Lopez, R. (2003). Defining and classifying periodontitis: need for a paradigm shift? European Journal of Oral Sciences 111, 2-6.
Berglundh, T., Zitzmann, N.U., and Donati, M. (2011). Are peri-implantitis lesions different from periodontitis lesions? Journal of Clinical Periodontology 38, 188-202.
Bullon, P., Fioroni, M., Goteri, G., Rubini, C., and Battino, M. (2004). Immunohistochemical analysis of soft tissues in implants with healthy and peri-implantitis condition, and aggressive periodontitis. Clinical Oral Implants Research 15, 553-559.
Carcuac, O., and Berglundh, T. (2014). Composition of Human Peri-implantitis and Periodontitis Lesions. Journal of Dental Research 93, 1083-1088.
Dalakas, M.C. (2008). B cells as therapeutic targets in autoimmune neurological disorders. Nature Clinical Practice Neurology 4, 557-567.
Dentino, A., Lee, S., Mailhot, J., and Hefti, A.F. (2013). Principles of periodontology. Periodontology 2000 61, 16-53.
Eke, P.I., Dye, B.A., Wei, L., Slade, G.D., Thornton-Evans, G.O., Borgnakke, W.S., Taylor, G.W., Page, R.C., Beck, J.D., and Genco, R.J. (2015). Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012. Journal of Periodontology 86, 611-622.
Esposito, M., Thomsen, P., Ericson, L.E., Sennerby, L., and Lekholm, U. (2000). Histopathologic Observations on Late Oral Implant Failures. Clinical Implant Dentistry and Related Research 2, 18-32.
Flemmig, T.F. (1999). Periodontitis. Annals of Periodontology 4, 32-37.
Fransson, C., Wennström, J., and Berglundh, T. (2008). Clinical characteristics at implants with a history of progressive bone loss. Clinical Oral Implants Research 19, 142-147.
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K., Tanaka, M., Kishimoto, K., Matsuki, Y., Murakami, M., Ichisaka, T., Murakami, H., et al. (2005). Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin. Science 307, 426-430.
Garten, A., Schuster, S., Penke, M., Gorski, T., de Giorgis, T., and Kiess, W. (2015). Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 11, 535-546.
Goodman, S.B., Ma, T., Chiu, R., Ramachandran, R., and Smith, R.L. (2006). Effects of orthopaedic wear particles on osteoprogenitor cells. Biomaterials 27, 6096-6101.
Harris, L.G., Mead, L., Müller-Oberländer, E., and Richards, R.G. (2006). Bacteria and cell cytocompatibility studies on coated medical grade titanium surfaces. Journal of Biomedical Materials Research Part A 78A, 50-58.
Heitz-Mayfield, L.J., and Mombelli, A. (2014). The therapy of peri-implantitis: a systematic review. The International journal of oral & maxillofacial implants 29 Suppl, 325-345.
Heitz-Mayfield, L.J.A., and Lang, N.P. (2010). Comparative biology of chronic and aggressive periodontitis vs. peri-implantitis. Periodontology 2000 53, 167-181.
Karoussis, I.K., Brägger, U., Salvi, G.E., Bürgin, W., and Lang, N.P. (2004). Effect of implant design on survival and success rates of titanium oral implants: a 10-year prospective cohort study of the ITI® Dental Implant System
Der Einfluss des Implantatdesigns auf die Überlebens- und Erfolgsrate von Titanimplantaten: Eine Langzeitstudie des ITI®-Systems über 10 Jahre. Clinical Oral Implants Research 15, 8-17.
Koltai, E., Szabo, Z., Atalay, M., Boldogh, I., Naito, H., Goto, S., Nyakas, C., and Radak, Z. (2010). Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats. Mechanisms of Ageing and Development 131, 21-28.
Leonhardt, Å., Dahlén, G., and Renvert, S. (2003). Five-Year Clinical, Microbiological, and Radiological Outcome Following Treatment of Peri-Implantitis in Man. Journal of Periodontology 74, 1415-1422.
Lindhe, J., Meyle, J., and on behalf of Group, D.o.t.E.W.o.P. (2008). Peri-implant diseases: Consensus Report of the Sixth European Workshop on Periodontology. Journal of Clinical Periodontology 35, 282-285.
Máximo, M.B., De Mendonça, A.C., Renata Santos, V., Figueiredo, L.C., Feres, M., and Duarte, P.M. (2009). Short-term clinical and microbiological evaluations of peri-implant diseases before and after mechanical anti-infective therapies. Clinical Oral Implants Research 20, 99-108.
Mombelli, A., and Lang, N.P. (1998). The diagnosis and treatment of peri-implantitis. Periodontology 2000 17, 63-76.
Mombelli, A., Müller, N., and Cionca, N. (2012). The epidemiology of peri-implantitis. Clinical Oral Implants Research 23, 67-76.
Moschen, A.R., Kaser, A., Enrich, B., Mosheimer, B., Theurl, M., Niederegger, H., and Tilg, H. (2007). Visfatin, an Adipocytokine with Proinflammatory and Immunomodulating Properties. The Journal of Immunology 178, 1748-1758.
Mouhyi, J., Dohan Ehrenfest, D.M., and Albrektsson, T. (2012). The peri-implantitis: implant surfaces, microstructure, and physicochemical aspects. Clin Implant Dent Relat Res 14, 170-183.
Nau, G.J., Richmond, J.F., Schlesinger, A., Jennings, E.G., Lander, E.S., and Young, R.A. (2002). Human macrophage activation programs induced by bacterial pathogens. Proceedings of the National Academy of Sciences of the United States of America 99, 1503-1508.
Nogueira, A.V.B., Nokhbehsaim, M., Eick, S., Bourauel, C., Jäger, A., Jepsen, S., Cirelli, J.A., and Deschner, J. (2013). Regulation of visfatin by microbial and biomechanical signals in PDL cells. Clinical Oral Investigations 18, 171-178.
O’Connell, F.P., Pinkus, J.L., and Pinkus, G.S. (2004). CD138 (Syndecan-1), a Plasma Cell Marker. Immunohistochemical Profile in Hematopoietic and Nonhematopoietic Neoplasms 121, 254-263.
Ognjanovic, S., Bao, S., Yamamoto, S.Y., Garibay-Tupas, J., Samal, B., and Bryant-Greenwood, G.D. (2001). Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. Journal of Molecular Endocrinology 26, 107-117.
Olmedo, D.G., Duffo, G., Cabrini, R.L., and Guglielmotti, M.B. (2008). Local effect of titanium implant corrosion: an experimental study in rats. International journal of oral and maxillofacial surgery 37, 1032-1038.
Olszanecka-Glinianowicz, M., Owczarek, A., Bożentowicz-Wikarek, M., Brzozowska, A., Mossakowska, M., Zdrojewski, T., Grodzicki, T., Więcek, A., and Chudek, J. (2014). Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population – results from the PolSenior substudy. Metabolism 63, 1409-1418.
Persson, G.R., Samuelsson, E., Lindahl, C., and Renvert, S. (2010). Mechanical non-surgical treatment of peri-implantitis: a single-blinded randomized longitudinal clinical study. II. Microbiological results. Journal of Clinical Periodontology 37, 563-573.
Piattelli, A., Scarano, A., and Piattelli, M. (1998). Histologic Observations on 230 Retrieved Dental Implants: 8 Years' Experience (1989–1996). Journal of Periodontology 69, 178-184.
Pradeep, A.R., Raghavendra, N.M., Prasad, M.V.R., Kathariya, R., Patel, S.P., and Sharma, A. (2011). Gingival Crevicular Fluid and Serum Visfatin Concentration: Their Relationship in Periodontal Health and Disease. Journal of Periodontology 82, 1314-1319.
Renvert, S., Samuelsson, E., Lindahl, C., and Persson, G.R. (2009). Mechanical non-surgical treatment of peri-implantitis: a double-blind randomized longitudinal clinical study. I: clinical results. Journal of Clinical Periodontology 36, 604-609.
Revollo, J.R., Korner, A., Mills, K.F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R.R., et al. (2007). Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell metabolism 6, 363-375.
Romacho, T., Villalobos, L.A., Cercas, E., Carraro, R., Sanchez-Ferrer, C.F., and Peiro, C. (2013). Visfatin as a novel mediator released by inflamed human endothelial cells. PloS one 8, e78283.
Romeo, E., Ghisolfi, M., Murgolo, N., Chiapasco, M., Lops, D., and Vogel, G. (2005). Therapy of peri-implantitis with resective surgery. Clinical Oral Implants Research 16, 9-18.
Serino, G., and Turri, A. (2011). Outcome of surgical treatment of peri-implantitis: results from a 2-year prospective clinical study in humans. Clinical Oral Implants Research 22, 1214-1220.
Shin-ichiro, I. (2009). Nicotinamide Phosphoribosyltransferase (Nampt): A Link Between NAD Biology, Metabolism, and Diseases. Current Pharmaceutical Design 15, 20-28.
Sun, Z., Lei, H., and Zhang, Z. (2013). Pre-B Cell Colony Enhancing Factor (PBEF), a Cytokine with Multiple Physiological Functions. Cytokine & growth factor reviews 24, 433-442.
Suvan, J., D'Aiuto, F., Moles, D.R., Petrie, A., and Donos, N. (2011). Association between overweight/obesity and periodontitis in adults. A systematic review. Obesity Reviews 12, e381-e404.
Tawse-Smith, A., Ma, S., Siddiqi, A., Duncan, W.J., Girvan, L., and Hussaini, H.M. (2012). Titanium Particles in Peri-Implant Tissues: Surface Analysis and Histologic Response. Clinical Advances in Periodontics 2, 232-238.
Theodosios, D.F., Harpal, S.R., Christos, S.D., Moses, S.E., and Dimitri, P.M. (2010). Visfatin/PBEF and Atherosclerosis-Related Diseases. Current Vascular Pharmacology 8, 12-28.
Van Der Velden, U. (2005). Purpose and problems of periodontal disease classification. Periodontology 2000 39, 13-21.
Vogel, C., and Marcotte, E.M. (2012). Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nature reviews Genetics 13, 227-232.
Yoshino, J., Mills, Kathryn F., Yoon, Myeong J., and Imai, S.-i. (2011). Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metabolism 14, 528-536.