P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts
Ankita Agrawal1, Zanne Henriksen1, Susanne Syberg1
1Research Centre for Ageing and Osteoporosis, Department of Clinical Biochemistry, Rigshospitalet, Denmark.
Abstract:
The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling. We report that osteoblasts derived from human trabecular explants express a functional P2X7R capable of agonist-induced increase in intracellular calcium concentration and a positive permeability to fluorescent dyes. These osteoblasts are fully differentiated cells with alkaline phosphatase activity and the ability to form mineralized nodules. We show that the transcriptional regulation of osteoblastic markers can be modulated by P2X7R activity or blockade thereby influencing the differentiation, proliferation and bone matrix formation by these primary human osteoblasts. Finally, we demonstrate that the P2X7R is involved in propagation of mechanically-induced intercellular signaling in addition to the known mechanisms involving calcium signaling via P2Y2 receptors and gap junction.
Insights
The P2X7 receptor (P2X7R) is functional in human osteoblasts, influencing bone formation and cell signaling. This study reveals P2X7R
Area of Science:
- Bone Biology
- Cell Signaling
- Receptor Pharmacology
Background:
- The P2X7 receptor (P2X7R) regulates physiological functions, including bone metabolism.
- Previous studies focused on rodent models and cell lines, leaving the role in primary human osteoblasts unclear.
Purpose of the Study:
- To investigate P2X7R expression in human bone marrow stromal cells and primary osteoblasts.
- To determine P2X7R's function in human osteoblast differentiation, proliferation, and bone matrix formation.
- To explore P2X7R's role in mechanically-induced intercellular signaling.
Main Methods:
- Analysis of P2X7R expression in human trabecular osteoblasts.
- Assessment of calcium signaling and dye permeability upon P2X7R activation.
- Evaluation of osteoblastic marker gene expression and nodule formation.
- Investigation of P2X7R involvement in mechanical signaling pathways.
Main Results:
- Primary human osteoblasts express functional P2X7R, showing increased intracellular calcium and dye permeability.
- P2X7R activity modulates osteoblastic marker expression, influencing differentiation, proliferation, and matrix formation.
- P2X7R participates in mechanically-induced intercellular signaling.
Conclusions:
- P2X7R is a functional receptor in primary human osteoblasts, impacting bone formation.
- Targeting P2X7R offers potential therapeutic strategies for bone diseases.
- P2X7R plays a role in mechanotransduction in bone cells.
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