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Key Mechanism In Pathogenesis Of Osteoporosis Unraveled

Date:
May 20, 2009
Source:
Helmholtz Association of German Research Centres
Summary:
Osteoporosis, or bone loss, is a disease that is most common in the elderly population, affecting women more often than men. Until now, it was not clear exactly how the disease develops. Researchers have now elucidated a molecular mechanism which regulates the equilibrium between bone formation and bone resorption. They hope these findings will lead to new therapies for this bone disease.
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FULL STORY

Osteoporosis, or bone loss, is a disease that is most common in the elderly population, affecting women more often than men. Until now, it was not clear exactly how the disease develops. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now elucidated a molecular mechanism which regulates the equilibrium between bone formation and bone resorption. Dr. Jeske J. Smink, Dr. Valérie Bégay, and Professor Achim Leutz were able to show that two different forms of a gene switch – a short isoform and a long isoform – determine this process.

The MDC researchers hope these findings will lead to new therapies for this bone disease. 

In osteoporosis, excessive bone resorption occurs. The bones lose their density and are therefore prone to breakage. Even minor falls can lead to serious bone fractures. The interplay between two cell types determines bone density: bone forming cells (osteoblasts) and bone resorbing cells (osteoclasts). The equilibrium between these two cell types is strictly regulated to prevent the formation of either too much or too little bone.

LAP and LIP maintain the balance

Dr. Smink, Dr. Bégay, and Professor Leutz have now elucidated a complicated mechanism which maintains the equilibrium between bone formation and bone resorption. Here, the gene switch C/EBPbeta plays a major role. It exists in different forms, differing in length and number of building blocks. LAP is the term researchers use to denote the full-length isoform of C/EBPbeta, and LIP is the term for the short isoform.

LAP activates another gene switch (MafB) which suppresses the formation of bone resorbing osteoclasts. In contrast, LIP, suppresses this gene switch and thus enhances the proliferation and activity of the osteoclasts. As a result, the osteoclasts resorb more bone substance than is built by the osteoblasts. The researchers suspect that imbalance in the ratio between LAP and LIP plays a role in osteoporosis.

The activity of a signaling molecule – mTOR – determines which of the two isoforms LAP and LIP is formed. The abbreviation mTOR stands for mammalian Target of Rapamycin. The drug rapamycin inhibits mTOR and thus suppresses the formation of bone resorbing osteoclasts. Unfortunately, rapamycin has severe side-effects on the immune system. "In the future, it may be possible to develop new drugs that regulate the activity of mTOR and, thus, remedy the disturbance in osteoclast function," Professor Leutz said.


Story Source:

The above story is based on materials provided by Helmholtz Association of German Research Centres. Note: Materials may be edited for content and length.


Journal Reference:

  1. Smink et al. Transcription factor C/EBPβ isoform ratio regulates osteoclastogenesis through MafB. The EMBO Journal, 2009; DOI: 10.1038/emboj.2009.127

Cite This Page:

Helmholtz Association of German Research Centres. "Key Mechanism In Pathogenesis Of Osteoporosis Unraveled." ScienceDaily. ScienceDaily, 20 May 2009. <www.sciencedaily.com/releases/2009/05/090514125156.htm>.
Helmholtz Association of German Research Centres. (2009, May 20). Key Mechanism In Pathogenesis Of Osteoporosis Unraveled. ScienceDaily. Retrieved May 26, 2015 from www.sciencedaily.com/releases/2009/05/090514125156.htm
Helmholtz Association of German Research Centres. "Key Mechanism In Pathogenesis Of Osteoporosis Unraveled." ScienceDaily. www.sciencedaily.com/releases/2009/05/090514125156.htm (accessed May 26, 2015).

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