From rxpgnews.com

Pharmacology
Caspase-3 inhibitors accelerate osteoporosis
By Pankaj, US correspondent
Dec 16, 2004, 17:42

When our cells reach a certain age or state of cell health they undergo a programmed form of cell death known as apoptosis. This normal process, mediated by the enzyme caspase-3, helps maintain a balance between cell growth and cell death. Excessive apoptosis of osteoblasts and osteocytes � cells that aid the growth and development of bone � has been implicated as an important process that causes a loss of bone mineral density in patients with osteoporosis.

In the December 15 issue of the Journal of Clinical Investigation, Songtao Shi and colleagues from the Craniofacial and Skeletal Diseases Branch of the National Institutes of Health examined mice deficient in caspase-3 or mice treated with a drug that inhibits caspase-3 activity, in addition to human bone marrow stromal stem cells (BMSSCs) treated with a caspase-3 inhibitor. Bone defects, including decreased bone mineral density, observed in caspase-3�deficient mice were due to decreased BMSSC maturation. The caspase-3 inhibitor was found to accelerate bone loss in mice and also block the formation of human BMSSCs.

The study offers a novel concept of how caspase-3 deficiency alters the development of stem cells leading to osteoporosis.

Given the demonstrated influence of the caspase-3 inhibitor on bone mineral density, the authors highlight the necessity for careful consideration of any future application of caspase-3 inhibitors � some of which are currently being assessed in animal studies for the treatment of some degenerative diseases � in the treatment of human disease. This caution would apply particularly to postmenopausal women as such treatment may adversely affect their bone mineral density.



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