Leptin reduces in vitro cementoblast mineralization and survival as well as induces PGE2 release by ERK1/2 commitment

Abstract

Objectives Juvenile obesity is a complex clinical condition that is present more and more frequently in the daily orthodontic practice. Over-weighted patients have an impaired bone metabolism, due in part to their increased levels of circulating adipokines. Particularly, leptin has been reported to play a key role in bone physiology. Leptin is ubiquitously present in the body, including blood, saliva, and crevicular fluid. If, and to what extent, it could influence the reaction of cementoblasts during orthodontic-induced forces is yet unknown. Material and methods OCCM-30 cementoblasts were cultivated under compressive forces using different concentrations of leptin. The expression of ObR, Runx-2, Osteocalcin, Rank-L, Sost, Caspase 3, 8, and 9 were analyzed by RT-PCR. Western blots were employed for protein analysis. The ERK1/2 antagonist FR180204 (Calbiochem) was used and cPLA2 activation, PGE2, and cytochrome C release were further evaluated. Results In vitro, when compressive forces are applied, leptin promotes ERK1/2 phosphorylation, as well as upregulates PGE2 and caspase 3 and caspase 9 on OCCM cells. Blockade of ERK1/2 impairs leptin-induced PGE2 secretion and reduced caspase 3 and caspase 9 expression. Conclusions Leptin influences the physiological effect of compressive forces on cementoblasts, exerting in vitro a proinflammatory and pro-apoptotic effect. Clinical relevance Our findings indicate that leptin exacerbates the physiological effect of compressive forces on cementoblasts promoting the release of PGE2 and increases the rate of cell apoptosis, and thus, increased levels of leptin may influence the inflammatory response during orthodontically induced tooth movement.

Adiponectin Interacts In-Vitro With Cementoblasts Influencing Cell Migration, Proliferation and Cementogenesis Partly Through the MAPK Signaling Pathway

“…In a previous study, we have shown that blockade of ERK1/2 impairs leptin-induced Caspase 3 and Caspase 9 expression on OCCM-30 cells ( Ruiz-Heiland et al, 2020 ). ( Kadowaki et al, 2006 ) observed that Adiponectin induces osteogenesis via P38 through AdipoR1, but not AdipoR2 on C3H10/T2 cells up-regulating the expression of Runx-2 ( Kadowaki et al, 2006 ).…”

Compressive force regulates GSK-3β in osteoclasts contributing to alveolar bone resorption during orthodontic tooth movement in vivo

“…When the process reaches a certain balance, the normal morphology and function of alveolar bone can be maintained. Additionally, one of the most important factors in orthodontic tooth movement is bone resorption caused by osteoclasts [ 12 ]. Recently, many studies have focused on how osteoclast differentiation influences orthodontic tooth movement and the mechanism behind this process [ 13 ].…”

Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

“…Meanwhile, M1 participates in the expression of cytokines, such as PGE2, IL-1β, TNF-α, IL-6 and IL-12, which are considered to be crucial players in the progression of PD and bone absorption. Among them, PGE2 is the most powerful stimulating factor of periodontal bone resorption, mediating various destruction processes of alveolar bone and cementum, such as reducing the mineralization and survival ability of osteoblasts, mediating the formation of osteoclasts, and stimulating the transformation of cementoblasts into cementum cells ( 54 , 55 ). LPS is an activator of IL-1β expression in M1, and IL-1β and TNF-α can also activate M1 to produce IL-1β, promoting the activation and differentiation of osteoclasts and ultimately causing bone resorption ( 56 ); TNF-α can also induce RANKL production by T cells and B cells ( 32 ).…”