FNDC5/irisin is expressed and regulated differently in human periodontal ligament cells, dental pulp stem cells and osteoblasts

Yang Yang,Helen Pullisaar,Maria A Landin,Catherine Anne Heyward,Maria Schröder,Tianxiang Geng,Maria Grano,Janne Elin Reseland

doi:10.1016/j.archoralbio.2021.105061

Yang Yang, Helen Pullisaar + Show 6 more

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https://doi.org/10.1016/j.archoralbio.2021.105061

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Abstract

ObjectiveTo examine the expression and regulation of fibronectin type III domain-containing protein 5/irisin (FNDC5/irisin) in primary human periodontal ligament (hPDL) cells, dental pulp stem cells (hDPCs) and osteoblasts (hOBs). MethodsFNDC5/irisin was identified in sections of paraffin embedded rat maxillae, cryo-sections of 3D cultured spheroids hPDL cells, hDPCs and hOBs, 2D cultured hPDL cells, hDPCs and hOBs by immunohistochemistry. The expression of FNDC5/irisin was identified by qPCR, followed by sequencing of the qPCR product. Regulation of FNDC5/irisin expression in hPDL cells, hDPCs and hOBs were evaluated after administration of different concentrations of irisin and all-trans retinoic acid (ATRA). qPCR and ELISA were used to identify expression and secretion of FNDC5/irisin in odontoblast-like differentiation of hDPCs. ResultsFNDC5/irisin was confirmed to be present in rat periodontium and dental pulp regions, as well as in 2D and 3D cultured hPDL cells, hDPCs and hOBs. BLAST analyses verified the generated nucleotide alignments matched human FNDC5/irisin. FNDC5/irisin gene expression was enhanced during odontoblast-like differentiation of hDPCs whereas the secretion of the protein was decreased compared to control. The protein signals in rat periodontal and pulpal tissues were higher than that of alveolar bone, and the expression of FNDC5/irisin was differently regulated by recombinant irisin and ATRA in hPDL cells and hDPCs compared to hOBs. ConclusionsFNDC5/irisin expression was verified in rodent periodontium and dental pulp, and in hPDL cells, hDPCs and hOBs. The FNDC5/irisin expression was regulated by recombinant irisin and ATRA. Finally, expression and secretion of FNDC5/irisin were affected during odontoblast-like differentiation of hDPCs.

Highlights

Irisin is a newly identified polypeptide hormone that is proteolyti cally cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), released into circulation in response to physical activity, and identified to be present in skeletal muscle and blood plasma (Bostrom et al, 2012)
To the authors’ best knowledge, the present research is the first to confirm that FNDC5/irisin is expressed in human periodontal ligament (hPDL) cells, human dental pulp stem cells (hDPCs) and Human osteoblasts (hOBs)
The sequence alignment of the amplified irisin product from hPDL cells matched with the human FNDC5 gene, which serves as evi dence to confirm the expression of FNDC5/irisin in hPDL cells

Summary

Introduction

Irisin is a newly identified polypeptide hormone that is proteolyti cally cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), released into circulation in response to physical activity, and identified to be present in skeletal muscle and blood plasma (Bostrom et al, 2012). The systematic location and expression of FNDC5/irisin in other human tissues was first comprehensively exam ined by Aydin et al, who identified FNDC5/irisin to be expressed in perimysium, endomysium, testis, pancreas, spleen, liver, brain, stomach and cardiac tissues. They defined the nerve sheaths spreading within human skeletal muscles to be the main producers of FNDC5/irisin (Aydin, Kuloglu et al, 2014). It would be of interest to investigate if FNDC5/irisin is expressed in oral tissues and cells sup porting tooth attachment

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