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Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP
- Source :
- Proceedings of the National Academy of Sciences. 88:2936-2940
- Publication Year :
- 1991
- Publisher :
- Proceedings of the National Academy of Sciences, 1991.
-
Abstract
- The osteoclast is unique in its ability to resorb bone, and excessive osteoclastic activity has been implicated in osteoporosis, Paget disease of bone, rheumatoid arthritis, and the growth of metastases in bone. The activity of this cell is controlled by the main circulating inhibitor, calcitonin, in association with locally produced modulators. We show that nitric oxide (NO) may be an important member of the latter group. NO is produced by the vascular endothelium and nervous system and is involved in both neurotransmission and the regulation of blood pressure. However, our results show that the autocoid is also a potent inhibitor of osteoclast function. NO (30 microM) produced a decrease to approximately 50% of the original osteoclast spread area. Similar effects were also produced by 3-morpholinosydnonimine or sodium nitroprusside, reagents that spontaneously release NO. These shape changes were associated with a reduction of bone resorption after a 24-hr incubation of isolated osteoclasts on devitalized bone slices. NO is thought to act by stimulating guanylate cyclase, with a consequent increase in cyclic GMP, but a different mode of action is likely in the osteoclast since dibutyryl or 8-bromo cyclic GMP have no effect. It should be noted that calcitonin can produce similar changes in shape and activity but is associated with an increase in osteoclast intracellular calcium and cessation of membrane movement; neither of these is produced by NO, suggesting that its mode of action is different. The abundance of NO-producing endothelial cells in bone marrow and their proximity to osteoclasts suggests that marrow endothelial cells may play a physiological role in the regulation of osteoclastic activity.
- Subjects :
- Calcitonin
musculoskeletal diseases
medicine.medical_specialty
Vasodilator Agents
Osteoclasts
Nitric Oxide
Calcium in biology
Bone resorption
Nitric oxide
chemistry.chemical_compound
Cytosol
Osteoclast
Internal medicine
Dibutyryl Cyclic GMP
medicine
Animals
Bone Resorption
Mode of action
Cyclic GMP
Cells, Cultured
Multidisciplinary
Ionomycin
Cell Membrane
Rats, Inbred Strains
Rats
Resorption
Kinetics
Endocrinology
medicine.anatomical_structure
Animals, Newborn
chemistry
Molsidomine
Calcium
Bone marrow
Research Article
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....ef8a50011dd39ec78843953e79fc5683