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Leptin effects on the regenerative capacity of human periodontal cells.

Nokhbehsaim M, Keser S, Nogueira AV, Jäger A, Jepsen S, Cirelli JA, Bourauel C, Eick S, Deschner J - Int J Endocrinol (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany ; Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of interleukin (IL)-1β, cyclic tensile strain (CTS), F. nucleatum (Fn), P. gingivalis (Pg), and T. denticola (Td) on leptin mRNA in PDL cells at 3 d (a). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS and Fn on the protein level of leptin released from cells into the medium at 3 d (b). Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effects of IL-1β, CTS, Fn, Pg, and Td on leptin receptor (LEPR) mRNA in PDL cells at 1 d and 3 d (c). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS (d) and Fn, Pg, and Td (e) on LEPR protein in lysates from PDL cells at 1 d. Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effect of leptin (3 ng/mL) on its own mRNA and that of its receptor in PDL cells at 1 d and 3 d (f). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control. Effect of leptin (3 ng/mL) on IL-6, tumor necrosis factor (TNF) α, and cyclooxygenase (COX) 2 mRNA in PDL cells at 3 d (g). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control.
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fig5: Effect of interleukin (IL)-1β, cyclic tensile strain (CTS), F. nucleatum (Fn), P. gingivalis (Pg), and T. denticola (Td) on leptin mRNA in PDL cells at 3 d (a). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS and Fn on the protein level of leptin released from cells into the medium at 3 d (b). Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effects of IL-1β, CTS, Fn, Pg, and Td on leptin receptor (LEPR) mRNA in PDL cells at 1 d and 3 d (c). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS (d) and Fn, Pg, and Td (e) on LEPR protein in lysates from PDL cells at 1 d. Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effect of leptin (3 ng/mL) on its own mRNA and that of its receptor in PDL cells at 1 d and 3 d (f). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control. Effect of leptin (3 ng/mL) on IL-6, tumor necrosis factor (TNF) α, and cyclooxygenase (COX) 2 mRNA in PDL cells at 3 d (g). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control.

Mentions: Next, we sought to examine if and under what conditions leptin and LEPR are produced in PDL cells. Leptin was constitutively expressed and this constitutive expression was significantly downregulated by IL-1β, CTS, F. nucleatum, P. gingivalis, and T. denticola at 1 d (data not shown) and 3 d (Figure 5(a)). The inhibitory effects were also found at protein level, as evidenced by the reduced protein levels of leptin released from cells exposed to CTS or F. nucleatum at 3 d (Figure 5(b)). Similar results were also observed for LEPR. Although IL-1β had no significant effect on the receptor expression, CTS, F. nucleatum, P. gingivalis, and T. denticola inhibited significantly LEPR at both time points (Figure 5(c)). In addition, CTS, F. nucleatum, P. gingivalis, and T. denticola reduced significantly the cellular LEPR protein level as measured in cell lysates at 1 d (Figures 5(d) and 5(e)). Since our experiments revealed that leptin is also produced by PDL cells, we wondered how leptin would affect its own expression and that of its receptor. As shown in Figure 5(f), leptin had no effect on its own expression, but caused a significant reduction of LEPR expression at 3 d.


Leptin effects on the regenerative capacity of human periodontal cells.

Nokhbehsaim M, Keser S, Nogueira AV, Jäger A, Jepsen S, Cirelli JA, Bourauel C, Eick S, Deschner J - Int J Endocrinol (2014)

Effect of interleukin (IL)-1β, cyclic tensile strain (CTS), F. nucleatum (Fn), P. gingivalis (Pg), and T. denticola (Td) on leptin mRNA in PDL cells at 3 d (a). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS and Fn on the protein level of leptin released from cells into the medium at 3 d (b). Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effects of IL-1β, CTS, Fn, Pg, and Td on leptin receptor (LEPR) mRNA in PDL cells at 1 d and 3 d (c). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS (d) and Fn, Pg, and Td (e) on LEPR protein in lysates from PDL cells at 1 d. Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effect of leptin (3 ng/mL) on its own mRNA and that of its receptor in PDL cells at 1 d and 3 d (f). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control. Effect of leptin (3 ng/mL) on IL-6, tumor necrosis factor (TNF) α, and cyclooxygenase (COX) 2 mRNA in PDL cells at 3 d (g). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control.
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Related In: Results  -  Collection

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fig5: Effect of interleukin (IL)-1β, cyclic tensile strain (CTS), F. nucleatum (Fn), P. gingivalis (Pg), and T. denticola (Td) on leptin mRNA in PDL cells at 3 d (a). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS and Fn on the protein level of leptin released from cells into the medium at 3 d (b). Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effects of IL-1β, CTS, Fn, Pg, and Td on leptin receptor (LEPR) mRNA in PDL cells at 1 d and 3 d (c). Untreated cells served as control. Mean ± SEM (n = 9); *significantly (P < 0.05) different from control. Effects of CTS (d) and Fn, Pg, and Td (e) on LEPR protein in lysates from PDL cells at 1 d. Untreated cells served as control. Mean ± SEM (n = 18); *significant (P < 0.05) difference between groups. Effect of leptin (3 ng/mL) on its own mRNA and that of its receptor in PDL cells at 1 d and 3 d (f). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control. Effect of leptin (3 ng/mL) on IL-6, tumor necrosis factor (TNF) α, and cyclooxygenase (COX) 2 mRNA in PDL cells at 3 d (g). Untreated cells served as control. Mean ± SEM (n = 18); *significantly (P < 0.05) different from control.
Mentions: Next, we sought to examine if and under what conditions leptin and LEPR are produced in PDL cells. Leptin was constitutively expressed and this constitutive expression was significantly downregulated by IL-1β, CTS, F. nucleatum, P. gingivalis, and T. denticola at 1 d (data not shown) and 3 d (Figure 5(a)). The inhibitory effects were also found at protein level, as evidenced by the reduced protein levels of leptin released from cells exposed to CTS or F. nucleatum at 3 d (Figure 5(b)). Similar results were also observed for LEPR. Although IL-1β had no significant effect on the receptor expression, CTS, F. nucleatum, P. gingivalis, and T. denticola inhibited significantly LEPR at both time points (Figure 5(c)). In addition, CTS, F. nucleatum, P. gingivalis, and T. denticola reduced significantly the cellular LEPR protein level as measured in cell lysates at 1 d (Figures 5(d) and 5(e)). Since our experiments revealed that leptin is also produced by PDL cells, we wondered how leptin would affect its own expression and that of its receptor. As shown in Figure 5(f), leptin had no effect on its own expression, but caused a significant reduction of LEPR expression at 3 d.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany ; Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany.

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.

No MeSH data available.


Related in: MedlinePlus