Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP - PubMed (original) (raw)

Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP

I MacIntyre et al. Proc Natl Acad Sci U S A. 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.

PubMed Disclaimer

Cited by

Endogenous n-3 fatty acids protect ovariectomy induced bone loss by attenuating osteoclastogenesis.
Rahman MM, Bhattacharya A, Banu J, Kang JX, Fernandes G. Rahman MM, et al. J Cell Mol Med. 2009 Aug;13(8B):1833-44. doi: 10.1111/j.1582-4934.2009.00649.x. J Cell Mol Med. 2009. PMID: 20141608 Free PMC article.
Molecular aspects of osteoclast function.
Hall TJ, Chambers TJ. Hall TJ, et al. Inflamm Res. 1996 Jan;45(1):1-9. doi: 10.1007/BF02263497. Inflamm Res. 1996. PMID: 8821771 Review.
Inhalation of diesel engine exhaust increases bone mineral concentrations in growing rats.
Watanabe N, Nakamura T. Watanabe N, et al. Arch Environ Contam Toxicol. 1996 Mar;30(3):407-11. doi: 10.1007/BF00212301. Arch Environ Contam Toxicol. 1996. PMID: 8854972
Nitric oxide and bone.
van't Hof RJ, Ralston SH. van't Hof RJ, et al. Immunology. 2001 Jul;103(3):255-61. doi: 10.1046/j.1365-2567.2001.01261.x. Immunology. 2001. PMID: 11454054 Free PMC article. Review.
NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model.
Iwasaki T, Higashiyama M, Kuriyama K, Sasaki A, Mukai M, Shinkai K, Horai T, Matsuda H, Akedo H. Iwasaki T, et al. Jpn J Cancer Res. 1997 Sep;88(9):861-6. doi: 10.1111/j.1349-7006.1997.tb00462.x. Jpn J Cancer Res. 1997. PMID: 9369934 Free PMC article.

References

1. J Physiol. 1990 Oct;429:29-45 - PubMed
1. J Cyclic Nucleotide Res. 1977 Feb;3(1):23-35 - PubMed
1. Biosci Rep. 1990 Dec;10(6):493-507 - PubMed
1. Biosci Rep. 1990 Dec;10(6):547-56 - PubMed
1. Br J Pharmacol. 1987 Nov;92(3):639-46 - PubMed

Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP - PubMed (original) (raw)