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Purinergic transmitters inhibit bone formation by cultured osteoblasts
1Department of Anatomy and Developmental Biology, University College London, UK. s.jones@ucl.ac.uk
Bone
|November 14, 1997
Summary
Adenosine triphosphate (ATP) and parathyroid hormone (PTH) can affect bone cells. This study found that ATP and PTH inhibit bone formation in rat osteoblasts, suggesting a role in bone remodeling.
Area of Science:
- Bone Biology and Mineral Metabolism
- Cell Signaling and Purinergic Receptors
Background:
- Adenosine triphosphate (ATP) and parathyroid hormone (PTH) are known to influence osteoblast activity, including calcium levels and proliferation.
- Evidence suggests potential synergistic interactions between ATP and PTH in osteoblasts, highlighting the importance of purinoceptors in bone remodeling.
- The specific impact of purinoceptor agonists, like ATP, on appositional bone formation remains largely unknown.
Purpose of the Study:
- To investigate the effects of various purinoceptor agonists and parathyroid hormone (PTH) on appositional bone formation in vitro.
- To determine whether ATP and related nucleotides influence bone formation by osteoblasts.
- To elucidate the role of purinergic signaling in the regulation of bone formation.
Main Methods:
- A novel culture system was employed, enabling appositional bone formation within defined grooves on a substratum.
- Rat calvarial osteoblasts were treated with a range of substances including ATP, ATP gamma S, 2-MeSATP, UTP, adenosine, bovine PTH, rat PTH1-34, and rat PTHrP1-40.
- Bone formation was quantified by measuring the number, length, and area of Alizarin red-stained mineralized bone formed over 16-29 days.
Main Results:
- ATP gamma S, 2-MeSATP, and ATP significantly reduced the amount of bone formed.
- Adenosine showed no effect on bone formation, while UTP had either no effect or a stimulatory effect at a specific concentration (2 mumol/L).
- Both PTH and PTHrP completely inhibited bone formation within a 4-week culture period.
Conclusions:
- The findings support the existence of multiple P2 purinoceptor subtypes in bone.
- ATP, acting through purinoceptors, demonstrates an inhibitory effect on appositional bone formation by osteoblasts in vitro.
- This study provides the first evidence that ATP, similar to PTH and PTHrP, negatively regulates bone formation in osteoblasts.