title: Leptin effects on the regenerative capacity of human periodontal cells.
abstract: Obesity is increasing throughout the globe and characterized by excess adipose tissue, which represents a complex endocrine organ. Adipose tissue secrets bioactive molecules called adipokines, which act at endocrine, paracrine, and autocrine levels. Obesity has recently been shown to be associated with periodontitis, a disease characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium, and also with compromised periodontal healing. Although the underlying mechanisms for these associations are not clear yet, increased levels of proinflammatory adipokines, such as leptin, as found in obese individuals, might be a critical pathomechanistic link. The objective of this study was to examine the impact of leptin on the regenerative capacity of human periodontal ligament (PDL) cells and also to study the local leptin production by these cells. Leptin caused a significant downregulation of growth (TGFβ1, and VEGFA) and transcription (RUNX2) factors as well as matrix molecules (collagen, and periostin) and inhibited SMAD signaling under regenerative conditions. Moreover, the local expression of leptin and its full-length receptor was significantly downregulated by inflammatory, microbial, and biomechanical signals. This study demonstrates that the hormone leptin negatively interferes with the regenerative capacity of PDL cells, suggesting leptin as a pathomechanistic link between obesity and compromised periodontal healing.
authors.affiliation: Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany ; Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany.
authors.forename: Marjan
authors.initials: M
authors.lastname: Nokhbehsaim
authors.affiliation: Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany.
authors.forename: Sema
authors.initials: S
authors.lastname: Keser
authors.affiliation: Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany ; Department of Diagnosis and Surgery, School of Dentistry, UNESP, 14801-903 Araraquara, SP, Brazil.
authors.forename: Andressa Vilas Boas
authors.identifier: 0000-0002-2756-5947
authors.initials: AV
authors.lastname: Nogueira
authors.affiliation: Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany ; Department of Orthodontics, University of Bonn, 53111 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jäger
authors.affiliation: Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany ; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, 53111 Bonn, Germany.
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry, UNESP, 14801-903 Araraquara, SP, Brazil.
authors.forename: Joni Augusto
authors.identifier: 0000-0002-7082-9290
authors.initials: JA
authors.lastname: Cirelli
authors.affiliation: Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany ; Oral Technology, Center of Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bourauel
authors.affiliation: Department of Periodontology, Laboratory of Oral Microbiology, University of Bern, 3010 Bern, Switzerland.
authors.forename: Sigrun
authors.identifier: 0000-0002-4619-2461
authors.initials: S
authors.lastname: Eick
authors.affiliation: Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany ; Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany.
authors.forename: James
authors.identifier: 0000-0002-8808-8769
authors.initials: J
authors.lastname: Deschner