Osteoblasts are bone idle without Frizzled-9

Mar 14, 2011
Compared to wild-type (left), a vertebra from a Fzd9-null mouse (right) shows reduced calcein staining (green), indicating a decreased rate of bone formation. Credit: Albers, J., et al. 2011. J. Cell Biol. doi:10.1083/jcb.201008012

New research shows that the Wnt receptor Frizzled-9 (Fzd9) promotes bone formation, providing a potential new target for the treatment of osteoporosis. The study appears online on March 14 in The Journal of Cell Biology .

Adult bones are maintained by a balance of bone-forming osteoblasts and bone-resorbing osteoclasts. Although Wnt signaling affects this balance in mice and humans, the Wnt receptors involved remain unknown. A team of researchers led by Thorsten Schinke found that the Wnt receptor Fzd9 was upregulated during osteoblast differentiation and that mice lacking Fzd9 had fragile bones due to low rates of .

Fzd9-null osteoblasts differentiated normally, but they failed to mineralize their extracellular matrix. The loss of Fzd9 disrupted a non-canonical branch of the Wnt signaling pathway, resulting in reduced levels of the transcription factor STAT1, which was, in turn, required for the expression of several interferon-regulated genes. One of these genes en-coded a ubiquitin-like molecule called Isg15. Though little is known about Isg15's function, restoring its expression in Fzd9-null osteoblasts boosted matrix mineralization, whereas mice lacking Isg15 had similar bone defects to Fzd9-knockout animals.

Mice lacking one copy of Fzd9 also had low , suggesting that insufficient Fzd9 may cause the reduced seen in Williams-Beuren syndrome patients, who have a hemizygous deletion of the chromosomal region that includes the FZD9 gene. Schinke now wants to investigate whether boosting Fzd9 expression has the opposite effect to Fzd9 depletion and can stimulate bone formation. If so, Fzd9 would be an attractive for treating a variety of bone-loss disorders.

Explore further: Malaria transmission linked to mosquitoes' sexual biology

More information: Albers, J., et al. 2011. J. Cell Biol. doi:10.1083/jcb.201008012

add to favorites email to friend print save as pdf

Related Stories

Controlling bone formation to prevent osteoporosis

Sep 27, 2010

Aging disrupts the balance between bone formation and bone destruction, resulting in osteoporosis, which is characterized by reduced bone mass and increased risk of fracture. Recent data have suggested that this imbalance ...

Recommended for you

Malaria transmission linked to mosquitoes' sexual biology

13 hours ago

Sexual biology may be the key to uncovering why Anopheles mosquitoes are unique in their ability to transmit malaria to humans, according to researchers at Harvard T. H. Chan School of Public Health and University of Per ...

Intermediary neuron acts as synaptic cloaking device

14 hours ago

Neuroscientists believe that the connectome, a map of each and every connection between the millions of neurons in the brain, will provide a blueprint that will allow them to link brain anatomy to brain function. ...

Skeleton of cells controls cell multiplication

14 hours ago

A research team from Instituto Gulbenkian de Ciencia (IGC; Portugal), led by Florence Janody, in collaboration with Nicolas Tapon from London Research Institute (LRI; UK), discovered that the cell's skeleton ...

New study shows safer methods for stem cell culturing

Feb 25, 2015

A new study led by researchers at The Scripps Research Institute (TSRI) and the University of California (UC), San Diego School of Medicine shows that certain stem cell culture methods are associated with increased DNA mutations. ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.