AUTHOR=Yong Jiawen , von Bremen Julia , Ruiz-Heiland Gisela , Ruf Sabine 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.645005

DOI=10.3389/fcell.2021.645005

ISSN=2296-634X

ABSTRACT=<p>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 <italic>P38</italic>α, <italic>JNK1</italic>, <italic>ERK1</italic>, <italic>ERK2</italic>, and <italic>AdipoRs</italic> as well as pharmacological MAPK inhibition were performed. We found that compressive forces increase the expression of <italic>AdipoRs</italic>. Adiponectin and compression up-regulate <italic>P38</italic>α,<italic>JNK1</italic>, <italic>ERK1</italic>, and <italic>ERK2</italic> as well as β-<italic>catenin</italic> 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 <italic>AdipoRs</italic>, <italic>P38</italic>α, and <italic>JNK1</italic>, showing the interaction of single MAPK molecules and β-catenin signaling in response to compression or adiponectin. Silencing by a dominantly negative version of <italic>P38</italic>α and <italic>JNK1</italic> 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.</p>