Expression and function of the P2X7 receptor in human osteoblasts: The role of NFATc1 transcription factor.

Autor: Bergamin LS; Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy., Penolazzi L; Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy., Lambertini E; Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy., Falzoni S; Department of Medical Sciences, University of Ferrara, Ferrara, Italy., Sarti AC; Department of Medical Sciences, University of Ferrara, Ferrara, Italy., Molle CM; Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada., Gendron FP; Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada., De Bonis P; Department of Neurosurgery, S. Anna University Hospital, Ferrara, Italy., Di Virgilio F; Department of Medical Sciences, University of Ferrara, Ferrara, Italy., Piva R; Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2021 Jan; Vol. 236 (1), pp. 641-652. Date of Electronic Publication: 2020 Jun 24.
DOI: 10.1002/jcp.29891
Abstrakt: Bone mineralization is an orchestrated process by which mineral crystals are deposited by osteoblasts; however, the detailed mechanisms remain to be elucidated. The presence of P2X7 receptor (P2X7R) in immature and mature bone cells is well established, but contrasting evidence on its role in osteogenic differentiation and deposition of calcified bone matrix remains. To clarify these controversies in the present study, we investigated P2X7R participation in bone maturation. We demonstrated that the P2X7R is expressed and functional in human primary osteoblasts, and identified in the P2RX7 promoter several binding sites for transcription factors involved in bone mineralization. Of particular interest was the finding that P2X7R expression is enhanced by nuclear factor of activated T cells cytoplasmic 1 (NFATc1) overexpression, and accordingly, NFATc1 is recruited at the P2RX7 gene promoter in SaOS2 osteoblastic-like cells. In conclusion, our data provide further insights into the regulation of P2X7R expression and support the development of drugs targeting this receptor for the therapy of bone diseases.
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Databáze: MEDLINE