Human P2X7 Receptor Causes Cycle Arrest in RPMI-8226 Myeloma Cells to Alter the Interaction with Osteoblasts and Osteoclasts

Multiple myeloma is a malignant expansion of plasma cells and aggressively affects bone health. We show that P2X7 receptor altered myeloma growth, which affects primary bone cells in vitro. Expression on six human myeloma cell lines confirmed the heterogeneity associated with P2X7 receptor. Pharmaco...

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Published inCells (Basel, Switzerland) Vol. 9; no. 11; p. 2341
Main Authors Agrawal, Ankita, Kruse, Lars S, Vangsted, Annette J, Gartland, Alison, Jørgensen, Niklas R
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 22.10.2020
MDPI
Subjects
Cell cycle
Cell receptors
Multiple myeloma
myeloma
Observations
Osteoblasts
osteoclasts
P2X7 receptor
Physiological aspects
Denmark
myeloma
osteoblasts
P2X7 receptor
osteoclasts
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Summary:Multiple myeloma is a malignant expansion of plasma cells and aggressively affects bone health. We show that P2X7 receptor altered myeloma growth, which affects primary bone cells in vitro. Expression on six human myeloma cell lines confirmed the heterogeneity associated with P2X7 receptor. Pharmacology with 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) as agonist showed dose-dependent membranal pores on RPMI-8226 ( = 0.0027) and blockade with P2X7 receptor antagonists. Ca influx with increasing doses of BzATP ( = 0.0040) was also inhibited with antagonists. Chronic P2X7 receptor activation reduced RPMI-8226 viability ( = 0.0208). No apoptosis or RPMI-8226 death was observed by annexin V/propidium iodide (PI) labeling and caspase-3 cleavage, respectively. However, bromodeoxyuridine (BrdU) labelling showed an accumulation of RPMI-8226 in the S phase of cell cycle progression (61.5%, = 0.0114) with significant decline in G0/G1 (5.2%, = 0.0086) and G2/M (23.5%, = 0.0015) phases. As myeloma pathology depends on a positive and proximal interaction with bone, we show that P2X7 receptor on RPMI-8226 inhibited the myeloma-induced suppression on mineralization ( = 0.0286) and reversed the excessive osteoclastic resorption. Our results demonstrate a view of how myeloma cell growth is halted by P2X7 receptor and the consequences on myeloma-osteoblast and myeloma-osteoclast interaction in vitro.
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ISSN:2073-4409
2073-4409
DOI:10.3390/cells9112341