JCI online early table of contents: April 1, 2008

Osteoclasts and osteoblasts are cells that have important but opposing roles in the maintenance of bone density — osteoclasts mediate bone destruction, whereas osteoblasts mediate bone formation. The generation of these cells types is tightly regulated and when disturbed it can lead to bone diseases such as osteoporosis. New data, generated by Shao-Cong Sun and colleagues, at The University of Texas MD Anderson Cancer Center, Houston, have now identified a role for the protein CYLD in regulating the generation of osteoclasts (a process also known as osteoclastogenesis) in mice.

In the study, osteoclastogenesis was found to be dysregulated in mice lacking the protein CYLD and this was associated with severe osteoporosis. Further analysis revealed the mechanism behind these defects — precursors of osteoclasts isolated from CYLD-deficient mice were hyperresponsive to RANKL-induced development leading to the production of more and larger osteoclasts. The authors therefore concluded that CYLD negatively regulates osteoclast generation induced by the protein RANKL and that the gene containing the information required to make the CYLD protein might be a genetic factor involved in the development of inherited bone disorders.

TITLE: Deubiquitinating enzyme CYLD regulates RANK signaling and osteoclastogenesis in mice

AUTHOR CONTACT:
Shao-Cong Sun
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Phone: (713) 563-3218; Fax: (713) 563-3280; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34257

DERMATOLOGY: New model of fragile skin disorder

Dystrophic epidermolysis bullosa (DEB) is a disorder characterized by fragile skin and associated with trauma-induced blistering, progressive soft tissue scarring, and an increased risk of developing skin cancer. It is a genetic disorder caused by mutations in the gene containing the information for making the protein collagen VII. In a new study, Leena Bruckner-Tuderman and colleagues, at the University Medical Center Freiburg, Germany, have developed a mouse model of DEB that characterizes the human disease very well, leading them to suggest that analysis of these mice might help researchers develop new and effective approaches to treating individuals with DEB.

Mice were engineered to express only low levels of collagen VII, about 10% of normal levels, and were found to develop the characteristic symptoms of DEB, including repeated skin blistering that led to tissue scarring (also known as fibrosis), which was caused by cells known as myofibroblasts. When normal fibroblast cells (which can give rise to myofibroblasts) were injected into the skin of the mutant mice, the treated area of skin was resistant to trauma-induced damage. By contrast, untreated areas of skin in the same mice remained susceptible to trauma-induced damage. These data led the authors to suggest that fibroblast-based treatments might provide a new avenue for the development of therapeutic strategies for DEB.