New function for the protein Bcl-xL: It prevents bone breakdown

Sep 14, 2009

In blood cells, the protein Bcl-xL has a well-characterized role in preventing cell death by a process known as apoptosis. However, its function(s) in osteoclasts, cells that slowly breakdown bone (a process known as resorption), has not been determined. In addressing this issue, Sakae Tanaka and colleagues, at The University of Tokyo, Japan, have discovered that not only does Bcl-xL prevent osteoclast apoptosis in mice, it also negatively regulates the bone-resorbing activity of osteoclasts.

To determine the function of Bcl-xL in osteoclasts, the researchers generated mice lacking Bcl-xL only in osteoclasts. As in blood cells, Bcl-xL was shown to promote the survival of osteoclasts. Unexpectedly, however, the exhibited marked osteopenia at one year of age.

Further analysis indicated that the reduced bone mass was caused by increased osteoclast-mediated and identified a potential underlying mechanism. Specifically, Bcl-xL was found to decrease the production of extracellular matrix proteins, which bind cell surface integrin molecules, leading to the activation of c-Src signaling pathways that are already known to promote osteoclast-mediated bone resorption. Thus, in the absence of Bcl-xL, increased production of extracellular matrix proteins leads to increased osteoclast-mediated bone resorption.

More information: View the PDF of this article at: www.the-jci.org/article.php?id=39819

Source: Journal of Clinical Investigation

Explore further: Gene mutation discovered in blood disorder

add to favorites email to friend print save as pdf

Related Stories

New therapeutic target for melanoma identified

Apr 16, 2009

A protein called Mcl-1 plays a critical role in melanoma cell resistance to a form of apoptosis called anoikis, according to research published this week in Molecular Cancer Research.

New clues about mitochondrial 'growth spurts'

Mar 02, 2009

Mitochondria are restless, continually merging and splitting. But contrary to conventional wisdom, the size of these organelles depends on more than fusion and fission, as Berman et al. show. Mitochondrial ...

Blood's clotting cells harbor 'ticking time bombs'

Mar 22, 2007

Fragments of cells in the blood known as platelets—which form blood clots and assist in wound healing—have internal “clocks” that act like ticking time bombs, predetermining their death from the moment they are born, ...

Recommended for you

Gene mutation discovered in blood disorder

7 minutes ago

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which ...

Airway muscle-on-a-chip mimics asthma

2 hours ago

The majority of drugs used to treat asthma today are the same ones that were used 50 years ago. New drugs are urgently needed to treat this chronic respiratory disease, which causes nearly 25 million people ...

Lost protein could prevent hardening of the arteries

6 hours ago

(Medical Xpress)—Researchers have found that when the protein matrix metalloproteinase-14 (MMP-14) is reduced or lost, white blood cells, known as macrophages, become good and could prevent hardening of ...

User comments : 0