Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts

Matteo Corradini; Marta Checchi; Marzia Ferretti; Francesco Cavani; Carla Palumbo; Vincenza Rita Lo Vasco; Matteo Corradini; Marta Checchi; Marzia Ferretti; Francesco Cavani; Carla Palumbo; Vincenza Rita Lo Vasco

doi:10.3934/biophy.2023004

AIMS Biophysics

2023, Volume 10, Issue 1: 25-49. doi: 10.3934/biophy.2023004

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Research article Special Issues

Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts

Section of Human Morphology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

Received: 11 November 2022 Revised: 21 December 2022 Accepted: 05 January 2023 Published: 29 January 2023

Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines.

In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122.

Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.
- phospholipase C,
- phosphoinositide,
- endoplasmic reticulum,
- human osteoblast,
- U-73122
Citation: Matteo Corradini, Marta Checchi, Marzia Ferretti, Francesco Cavani, Carla Palumbo, Vincenza Rita Lo Vasco. Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts[J]. AIMS Biophysics, 2023, 10(1): 25-49. doi: 10.3934/biophy.2023004

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Abstract

Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines.

In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122.

Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.

Acknowledgments

The present research work was funded by the University of Modena and Reggio Emilia, Grant COFIFAR2021DIPARTIMENTO to VR Lo Vasco.

Conflict of interest

All authors declare no conflicts of interest in this paper.

Author contribution

Matteo Corradini: formal analysis, methodology. Marta Checchi: methodology. Carla Palumbo: conceptualization, funding acquisition. Vincenza R. Lo Vasco: conceptualization, project administration, supervision, funding acquisition, writing.

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