{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:30:17Z","timestamp":1787023817388,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170970"],"award-info":[{"award-number":["81170970"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Gingipains are cysteine proteases produced by\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    , the predominant pathogen in chronic periodontitis. The present study aims to examine the role of gingipains in promoting apoptosis in osteoblasts.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Human calvarial osteoblasts and osteoblast MC3T3\u2010E1 cells were treated with 8.348 U\/L gingipains. Flow cytometry analysis and terminal deoxynucleotidyl transferase\u2010mediated deoxy\u2010UTP nick end labeling staining were used to detect cell apoptosis. Protein expression was examined by Western blotting, and gene expression was detected by real\u2010time polymerase chain reaction. Small interfering (si)RNA transfection was used to knock down BH3\u2010interacting domain death agonist (Bid) expression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Treatment with 8.348 U\/L gingipains from 4 to 72 hours increased apoptosis, accompanied by elevated cleaved caspase\u20103 levels. Notably, gingipain\u2010induced apoptosis was associated with increase of Bid and its truncated form, tBid, as well as p53. Transfection with Bid siRNA resulted in suppression of gingipain\u2010induced apoptosis. The p53 inhibitor, Pifithrin\u2010\u03b1, blocked the gingipain\u2010induced Bid. The ability of gingipains to stimulate p53 and Bid expression was mimicked by PD\u20100325901 and MK\u20102206, the specific extracellular signal\u2010regulated protein kinases (ERK) and protein kinase B (PKB) inhibitors, respectively. Furthermore, treatment with gingipains reduced phospho\u2010ERK and phospho\u2010PKB levels, an effect correlated to gingipain\u2010induced increase in p53 and tBid expression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The present findings suggest that Bid plays an essential role in gingipain\u2010induced osteoblast apoptosis, which is dependent on inhibition of ERK and PKB phosphorylation, followed by the activation of p53.\n                  <\/jats:p>","DOI":"10.1902\/jop.2017.160806","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T10:06:33Z","timestamp":1499681193000},"source":"Crossref","is-referenced-by-count":15,"title":["Signal\u2010Regulated Protein Kinases\/Protein Kinase B\u2010p53\u2010BH3\u2013Interacting Domain Death Agonist Pathway Regulates Gingipain\u2010Induced Apoptosis in Osteoblasts"],"prefix":"10.1002","volume":"88","author":[{"given":"Fuping","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangchen","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67728-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1998.tb02419.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2741\/2736"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1999.tb02273.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2000.027010769.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-107"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051X.1999.260810.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2001.72.4.517"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.135"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01140-05"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-6-26"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00405.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00393.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800910791859515"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400689"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103701200"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81590-1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2005.10.038"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.4.1244-1263.1998"},{"key":"e_1_2_8_21_1","first-page":"34","article-title":"The 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