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: Researchers unwind the mysteries of the cellular clock

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

Researchers unwind the mysteries of the cellular clock

10 hours ago

Human existence is basically circadian. Most of us wake in the morning, sleep in the evening, and eat in between. Body temperature, metabolism, and hormone levels all fluctuate throughout the day, and it ...

Signaling molecule crucial to stem cell reprogramming

10 hours ago

While investigating a rare genetic disorder, researchers at the University of California, San Diego School of Medicine have discovered that a ubiquitous signaling molecule is crucial to cellular reprogramming, a finding with ...

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.