Researchers discover gene that slows bone loss and promotes bone formation

August 12, 2014

(Medical Xpress)—Osteoporosis and aging-related bone loss is debilitating and painful. With a greater understanding of Wnt4 signaling, researchers are now closer to developing therapeutic agents that could slow down bone loss, regenerate lost bone and inhibit the inflammation associated with osteoporosis and aging-related bone diseases.

In the U.S. alone, approximately 54 million people over the age of 50 suffer from osteoporosis and aging-related bone loss, and the number of cases is expected to balloon to 64.4 million by 2030. Studies suggest that worldwide, 1 in 3 women over 50 will experience osteoporosis-related , as will 1 in 5 men.

Osteoporosis is caused when the process of , or the breakdown of bone, overpowers the process of bone formation. Bone loss is further exacerbated by chronic inflammation, often associated with aging. Most current osteoporosis medications are developed to slow bone loss by targeting the resorption. Researchers from the UCLA School of Dentistry have taken an important step toward a more effective treatment of osteoporosis. A research team led by Dr. Cun-Yu Wang, a UCLA School of Dentistry professor, is developing a novel therapeutic agent that not only slows down , but also promotes bone formation by suppressing inflammation in the .

The researchers discovered that a growth factor called Wnt4 that is secreted into the bone marrow effectively prevents bone loss in mouse models of osteoporosis and skeletal aging. It does this by inhibiting NF-кB signaling, a key pathway in the body's inflammatory processes.

Wang's team previously found that Wnt4 protein could promote ; in the new study, they created a strain of transgenic mice in which the Wnt4 gene was overexpressed in osteoblasts, or bone-forming cells. As expected, those mice exhibited increased compared with the control group, and they showed significantly less bone loss in an osteoporosis model. Surprisingly, the team discovered that Wnt4 protein not only promotes osteoblasts, but also suppresses the activity of osteoclasts, or bone-resorbing cells, as well as inflammation in the bone marrow.

In order to understand the mechanisms of the action of Wnt4 protein, the researchers investigated its effect on NF-κB signaling—a key part of the process during osteoclast formation and bone inflammation. Mice with hyperactive NF-κB signaling developed arthritis-like symptoms and showed bone loss, but cross-mating these mice with Wnt4 transgenic mice effectively alleviated these symptoms. Wnt4 also displayed a slower decline of bone mass associated with advanced age. The team went on to show that Wnt4 protein could inhibit osteoclast formation in vitro by removing a protein important for NF-κB activation.

Finally, to investigate the therapeutic use of Wnt4 for osteoporosis, the team generated osteoporosis in mice and introduced recombinant Wnt4 protein to those mice. They discovered a profound therapeutic effect of Wnt4 protein in mice with osteoporosis. Bone loss was markedly reduced among the group receiving Wnt4 injections, supporting the theory that recombinant Wnt4 protein could potentially be useful for treatment of and aging-related .

Explore further: Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

More information: Nature Medicine, www.nature.com/nm/journal/vaop … nt/full/nm.3586.html

Related Stories

Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

December 9, 2013
Bone homeostasis requires precise balance between deposition of new bone by osteoblasts and resorption of old bone by osteoclasts. Bone diseases, including osteoporosis and rheumatoid arthritis, are the result of increased ...

Identification of a molecule linking bone loss and bone formation

August 1, 2013
Bone integrity requires skeletal remodeling, which involves both bone formation and resorption. It has been previously shown that the formation of new bone is triggered by degradation of older bone. However, it is unknown ...

Bone loss associated with increased production of ROS

October 15, 2013
Bone is constantly being broken down and remodeled. Osteoporosis results when bone resorption outpaces bone regeneration. Production of reactive oxygen species, a form of oxidative stress, has been predicted to promote bone ...

MicroRNA that blocks bone destruction could offer new therapeutic target for osteoporosis

June 25, 2014
UT Southwestern cancer researchers have identified a promising molecule that blocks bone destruction and, therefore, could provide a potential therapeutic target for osteoporosis and bone metastases of cancer.

Common osteoporosis drug slows formation of new bone

April 17, 2013
Although the drug zoledronic acid slows bone loss in osteoporosis patients, it also boosts levels of a biomarker that stops bone formation, according to a recent study accepted for publication in The Endocrine Society's Journal ...

Proper stem cell function requires hydrogen sulfide

April 17, 2014
Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

0 comments

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.