Protease-activated receptor type 1 (PAR1) increases CEMP1 gene expression through MAPK/ERK pathway

Rovai, Emanuel Silva; Alves, Tomaz; Gasparoni, Letícia Miquelitto; França, Bruno Nunes de; Sipert, Carla Renata; Kantarcı, Alpdoğan; Holzhausen, Marinella

doi:10.1590/1807-3107bor-2022.vol36.0048

Cited by 3 publications

(1 citation statement)

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“…The protease-activated receptor type 1 (PAR 1 ) is a G protein-coupled cell membrane receptor that regulates several intracellular signaling pathways related to enhancement of osteogenic differentiation, increase in mineralized matrix deposition and upregulation of cementogenic gene expression as well 9 . PAR 1 activation plays a key role in osteogenesis and bone regeneration 5 , 10 by enhancing osteoblast proliferation and differentiation 11 , increasing the synthesis of osteoprotegerin (OPG) in periodontal ligament cells and reducing the inflammatory osteoclastogenesis induced by LPS 12 .…”

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confidence: 99%

Osteogenesis in human periodontal ligament stem cell sheets is enhanced by the protease-activated receptor 1 (PAR1) in vivo

Alves

Gasparoni

Balzarini

et al. 2022

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Human periodontal ligament stem cells (PDLSCs) have been studied as a promising strategy in regenerative approaches. The protease-activated receptor 1 (PAR 1 ) plays a key role in osteogenesis and has been shown to induce osteogenesis and increase bone formation in PDLSCs. However, little is known about its effects when activated in PDLSCs as a cell sheet construct and how it would impact bone formation as a graft in vivo. Here, PDLSCs were obtained from 3 patients. Groups were divided into control, osteogenic medium and osteogenic medium + PAR 1 activation by TFLLR-NH2 peptide. Cell phenotype was determined by flow cytometry and immunofluorescence. Calcium deposition was quantified by Alizarin Red Staining. Cell sheet microstructure was analyzed through light, scanning electron microscopy and histology and transplanted to Balb/c nude mice. Immunohistochemistry for bone sialoprotein (BSP), integrin β1 and collagen type 1 and histological stains (H&E, Van Giesson, Masson’s Trichrome and Von Kossa) were performed on the ex-vivo mineralized tissue after 60 days of implantation in vivo . Ectopic bone formation was evaluated through micro-CT. PAR 1 activation increased calcium deposition in vitro as well as BSP, collagen type 1 and integrin β1 protein expression and higher ectopic bone formation (micro-CT) in vivo.

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