Adiponectin as Well as Compressive Forces Regulate in vitro β-Catenin Expression on Cementoblasts via Mitogen-Activated Protein Kinase Signaling Activation

Abstract

We aimed to investigate the molecular effect that adiponectin exerts on cementoblasts especially in the presence of compressive forces. OCCM-30 cells (M. Somerman, NIH, NIDCR, United States) were used. Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and western blots were employed to verify if the mRNA and protein levels of adiponectin receptors (AdipoRs), mitogen-activated protein kinase (MAPK), and β-catenin signaling were influenced by compressive forces or adiponectin. Moreover, siRNAs targeting P38α, JNK1, ERK1, ERK2, and AdipoRs as well as pharmacological MAPK inhibition were performed. We found that compressive forces increase the expression of AdipoRs. Adiponectin and compression up-regulate P38α,JNK1, ERK1, and ERK2 as well as β-catenin gene expression. Western blots showed that co-stimuli activate the MAPK and β-catenin signaling pathways. MAPK inhibition alters the compression-induced β-catenin activation and the siRNAs targeting AdipoRs, P38α, and JNK1, showing the interaction of single MAPK molecules and β-catenin signaling in response to compression or adiponectin. Silencing by a dominantly negative version of P38α and JNK1 attenuates adiponectin-induced TCF/LEF reporter activation. Together, we found that light compressive forces activate β-catenin and MAPK signaling pathways. Adiponectin regulates β-catenin signaling principally by inactivating the GSK-3β kinase activity. β-Catenin expression was partially inhibited by MAPK blockade, indicating that MAPK plays a crucial role regulating β-catenin during cementogenesis. Moreover, adiponectin modulates GSK-3β and β-catenin mostly through AdipoR1. P38α is a key connector between β-catenin, TCF/LEF transcription, and MAPK signaling pathway.

High-intensity interval training ameliorate diabetes-induced disturbances in Alzheimer's-related factors in the hippocampus through adiponectin signaling

“…Our results showed increased expression of GSK3B in the hippocampus following T2D. Adiponectin can modulates the GSK3B signaling pathway [53] and evidence supports GSK3's role in producing some of AD's characteristic hallmarks, such as extracellular accumulation of amyloid-β protein (Aβ) and intra neuronal neuro brillary tangles composed of hyper-phosphorylated tau and in ammatory markers. These effects contribute to synaptic and neuronal loss and memory decline [55].…”

“…AMPK/SIRT1 and BDNF can directly affect intracellular Aβ production, Tau phosphorylation, and neurogenesis via regulating α-, β-,γ-secretases, and GSK3 [52]. Activated GSK-3, phosphorylates and thereby inactivates glycogen synthase, an enzyme that converts glucose to glycogen for storage [53] (Fig. 11).…”

Immunorthodontics: Role of HIF-1α in the Regulation of (Peptidoglycan-Induced) PD-L1 Expression in Cementoblasts under Compressive Force

“…Then, a glass cylinder (35 mm in diameter) with smooth surfaces was placed over the confluent cell layers for 24 h. The magnitude of compressive force applied was 2.4 gf/cm 2 . Previous investigations have proved that this mechanical compressive stress can effectively be applied by utilized in this experiment [1]. Cells cultured without glass disc served as the control cells.…”

“…Compression is one hallmark of the specific microenvironments induced by orthodontic compressive force (CF) during orthodontic tooth movement (OTM), due to its capability to affect the cementoblasts homeostasis [1]. During OTM, compressive force triggers inflammatory osteoclastogenic and remodeling processes in the periodontal ligament (PDL) to further create an immune suppressive hypoxic microenvironment, which impairs the process of OTM [2].…”

Hypoxia‐inducible factor 1‐alpha acts as a bridge factor for crosstalk between ERK1/2 and caspases in hypoxia‐induced apoptosis of cementoblasts

“…7 Obese patients have an impaired cementum metabolism, due in part to their altered levels of circulating adipokines. 13,14 Adipokines, produced mainly by adipocytes, which influence apoptosis and inflammatory responses of cementoblasts during OTM in obese individuals. 15 Thus, it is of vital importance to investigate the influence of adipokines on the apoptosis of cementoblasts under the experimental hypoxic setup.…”