Leptin effects on the regenerative capacity of human periodontal cells.
Marjan NokhbehsaimSema KeserAndressa Vilas Boas NogueiraAndreas JägerSøren JepsenJoni Augusto CirelliChristoph BourauelSigrun EickJames DeschnerPublished in: International journal of endocrinology (2014)
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.
Keyphrases
- induced apoptosis
- adipose tissue
- stem cells
- insulin resistance
- mesenchymal stem cells
- cell cycle arrest
- metabolic syndrome
- weight loss
- type diabetes
- cell therapy
- tissue engineering
- oxidative stress
- endothelial cells
- high fat diet
- signaling pathway
- gene expression
- poor prognosis
- epithelial mesenchymal transition
- bariatric surgery
- microbial community
- transforming growth factor
- body mass index
- bone marrow
- induced pluripotent stem cells
- physical activity
- obese patients