Delayed stimulation of bone resorption in vitro by phosphodiesterase inhibitors requires the presence of adenylate cyclase stimulation
Abstract
The effect on cyclic AMP levels and bone resorption by two methylxanthine cyclic AMP phosphodiesterase (PDE) inhibitors, isobutyl-methylxanthine (IBMX) and theophylline, and two non-xanthine PDE inhibitors, Ro 20-1724 and rolipram, was studied in cultured mouse calvarial bones. Cyclic AMP accumulation in calvarial bones increased when Ro 20-1724 (0.1 mmol/l) or rolipram (30 mumol/l) was present in culture medium in 2 h incubations, and when IBMX (0.3 mmol/l) or theophylline (3 mmol/l) was present in 4 h incubations. The cyclic AMP response to PDE-inhibitors could be completely abolished by the cyclooxygenase-inhibitor indomethacin (1 mumol/l). In 120 h cultures, IBMX, theophylline, Ro 20-1724 and rolipram stimulated the release of 45Ca from calvarial bones prelabelled in vivo with 45Ca. This stimulatory effect could not be seen when the endogenous production of prostaglandins was reduced by adding indomethacin (1 mumol/l), hydrocortisone (1 mumol/l) or meclofenamic acid (1 mumol/l) to culture medium. These concentrations of indomethacin, hydrocortisone and meclofenamic acid did not reduce PTH- (10 nmol/l) or choleratoxin-stimulated (0.1 micrograms/ml) 45Ca release from mouse calvarial bones cultured for 120 h. The stimulation of 45Ca release in long-term cultures by the PDE inhibitors could be demonstrated in the presence of indomethacin, provided adenylate cyclase was stimulated by forskolin (1-10 nmol/l). The stimulatory effect of 1 alpha (OH)D3 on 45Ca release could not…
Read the paper
Related studies
- Development of a crushable foam model for human trabecular bone
- Data-driven motion compensation in HR-pQCT.
- Modeling of structure, quality, and function in the orthodontic patient
- Exploring the mechanism of Heidihuang Pill in the treatment of osteoporosis based on network pharmacology, molecular docking, and experimental validation
- Effect of fabric on the accuracy of computed tomography-based finite element analyses of the vertebra
- Use of interventions involving virtual reality tasks during the climacteric: a systematic review
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.