{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:50:46Z","timestamp":1789372246567,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"New York State Office of Science, Technology and Academic Research (NYSTAR)","award":["A43273"],"award-info":[{"award-number":["A43273"]}]},{"name":"NYSTAR's Center of Advanced Technology"},{"name":"Research Foundation, Stony Brook University","award":["A37298"],"award-info":[{"award-number":["A37298"]}]},{"name":"Ministry of Higher Education and Scientific Research in Libya"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2017,4]]},"abstract":"\n Background and Objective<\/jats:title>\n \n Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a \u201cbidirectional manner\u201d, the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (\n CMC<\/jats:styled-content>\n ) 2.24.\n <\/jats:p>\n <\/jats:sec>\n \n Material and Methods<\/jats:title>\n \n Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and\n Escherichia coli<\/jats:italic>\n endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis.\n CMC<\/jats:styled-content>\n 2.24 was administered by oral gavage (30 mg\/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (\n n<\/jats:italic>\n = 6 rats\/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (\n MMP)<\/jats:styled-content>\n \u20102 and\n MMP<\/jats:styled-content>\n \u20109 by gelatin zymography;\n MMP<\/jats:styled-content>\n \u20108 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone\u2010resorptive cytokines [interleukin (\n IL)<\/jats:styled-content>\n \u20101\u03b2,\n IL<\/jats:styled-content>\n \u20106 and tumor necrosis factor\u2010\u03b1], were measured in gingival tissue extracts and serum by\n ELISA<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Systemic administration of\n CMC<\/jats:styled-content>\n 2.24 to diabetic rats with endotoxin\u2010induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri\u2010ketonic phenylaminocarbonyl curcumin (\n CMC<\/jats:styled-content>\n 2.24) appeared to reduce the pathologically excessive levels of inducible\n MMP<\/jats:styled-content>\n s to near\u2010normal levels, but appeared to have no significant effect on the constitutive\n MMP<\/jats:styled-content>\n s required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically,\n CMC<\/jats:styled-content>\n 2.24 also favorably affected extra\u2010oral connective tissues, skin and skeletal bone.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study supports our hypothesis that\n CMC<\/jats:styled-content>\n 2.24 is a potential therapeutic pleiotropic\n MMP<\/jats:styled-content>\n inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia\u2010 and bacteria\u2010induced connective tissue destruction.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jre.12381","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T13:22:38Z","timestamp":1459603358000},"page":"186-200","source":"Crossref","is-referenced-by-count":54,"title":["A novel chemically modified curcumin reduces inflammation\u2010mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects"],"prefix":"10.1111","volume":"52","author":[{"given":"M. S.","family":"Elburki","sequence":"first","affiliation":[{"name":"Department of Oral Biology and Pathology School of Dental Medicine Stony Brook University Stony Brook NY USA"},{"name":"Department of Periodontics Faculty of Dentistry Benghazi University Benghazi Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. D.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology School of Dental Medicine Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. G.","family":"Terezakis","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology School of Dental Medicine Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology School of Dental Medicine Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology School of Dental Medicine Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Pharmacological Sciences Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. M.","family":"Golub","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology School of Dental Medicine Stony Brook University Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.2001.6.1.91"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.2001.6.1.99"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.14219\/jada.archive.2003.0370"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500201"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500606"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pdi.1732"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1992.63.4s.338"},{"key":"e_1_2_7_9_1","first-page":"285","article-title":"Host modulation: conceptualization to clinical trials and integration into clinical practice","volume":"30","author":"Ryan M","year":"2002","journal-title":"CDA J"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn286"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v4i0.19227"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2014.130701"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515586353"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.22.4.272"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1988.tb01365.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.4.547"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.106"},{"key":"e_1_2_7_18_1","first-page":"1024","article-title":"Increased circulatory MMP\u20102 and MMP\u20109 levels and activities in patients with type 1 diabetes mellitus","volume":"73","author":"Shiau M","year":"2006","journal-title":"J Med"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2741\/2757"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-16-2-164"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S21751"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-9-35"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.10.006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2012.07.007"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.1998.3.1.51"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2342-y"},{"key":"e_1_2_7_27_1","first-page":"61","article-title":"Diabetes mellitus and periodontal disease\u2013a two\u2010way road: current concepts and future considerations (literature review)","volume":"9","author":"Velea OA","year":"2013","journal-title":"Eur Sci J"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/959471"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712802884295"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712802884240"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345780570032101"},{"key":"e_1_2_7_32_1","article-title":"Chemically\u2010modified curcumins and alveolar bone loss in diabetic rats","volume":"90","author":"Elburki MS","year":"2011","journal-title":"J Dent Res"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1994.tb01218.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb07692.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.080021"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1983.tb00331.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00890a010"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(78)90477-4"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm2.1958.311.1.41"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(72)90042-8"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00854a021"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118475"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2005.06.006"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/356841"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01603.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2011.01788.x"},{"issue":"5","key":"e_1_2_7_47_1","first-page":"467","article-title":"Regulation of monocyte\/macrophage metalloproteinase production by cytokines","volume":"64","author":"Wahl LM","year":"1993","journal-title":"J Periodontol"},{"key":"e_1_2_7_48_1","first-page":"345","article-title":"Cytokine regulation of matrix metalloproteinase activity and its regulatory dysfunction in disease","volume":"376","author":"Ries C","year":"1995","journal-title":"Biol Chem Hoppe Seyler"},{"key":"e_1_2_7_49_1","first-page":"614","article-title":"Alloxan diabetes and reduced bone density in rat mandible","volume":"5","author":"Ramamurthy NS","year":"1973","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1983.tb00388.x"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.4103\/0972-124X.76917"},{"key":"e_1_2_7_52_1","first-page":"303","article-title":"Local and systemic factors in periodontal disease increase matrix \u2010 degrading enzyme activities in rat gingiva: effect of micocycline therapy","volume":"91","author":"Chang KM","year":"1996","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1990.tb00923.x"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016306"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1995.tb01788.x"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890600800103"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050193"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.10.005"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb24729.x"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.1998.3.1.40"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1991.tb01649.x"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1992.tb01149.x"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1086\/515178"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2010.01342.x"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.154831"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000058700.41738.12"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510363367"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.14219\/jada.archive.2011.0165"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2011.06.023"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2011.06.024"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801497"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301977200"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12059"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6147899"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0174-173X(84)80040-0"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.11.7096"}],"container-title":["Journal of Periodontal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12381","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12381","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.12381","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T17:26:10Z","timestamp":1696267570000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jre.12381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":75,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,4]]}},"alternative-id":["10.1111\/jre.12381"],"URL":"https:\/\/doi.org\/10.1111\/jre.12381","archive":["Portico"],"relation":{},"ISSN":["0022-3484","1600-0765"],"issn-type":[{"value":"0022-3484","type":"print"},{"value":"1600-0765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}