Researchers identify a treatment for a rare bone loss disorder that might also lead to help for aging brittle bones
A possible ‘first-line’ treatment for a rare bone loss disease has been identified by a research team led by Tohoku University in Japan. The research findings, published in the journal Molecular Cell, could also provide insight into treating age-related osteoporosis.
Hajdu-Cheney syndrome is a rare genetic disease that leads to severe osteoporosis and developmental defects, including the reabsorption of bones in the hands and feet. The disease is associated with mutations in a particular gene, called NOTCH2, which codes for proteins involved with bone maintenance. The NOTCH2 proteins usually help balance destruction and construction essential for bone maintenance and repair. Mutations associated with Hajdu-Cheney syndrome upset that balance, but the exact mechanisms causing bone resorption have not been well understood.
Now, through a series of detailed tests, molecular biologist Hiroyuki Inuzuka and his colleagues have worked out the specific molecular pathway that results in Hajdu-Cheney syndrome.
They found that this particular NOTCH2 mutation does not maintain normal NOTCH2 protein abundance, with the help of another protein, called FBW7. To discover this, the researchers knocked out the gene for Fbw7 in the bones of mice. Without the gene and resulting protein, the mice had severe osteoporosis, much like people with Hajdu-Cheney syndrome — indicating that FBW7 is the primary regulator of this system.
They further determined that in humans with Hajdu-Cheney syndrome, the FBW7 protein was unable to bind to NOTCH2 proteins because the binding spot is missing in osteoclasts. This mutation allows the osteoclasts to over-operate, breaking down too much bone tissue.
The researchers were able to reverse bone loss in the knock-out mice with the elevated NOTCH2 by giving them a medication that blocks osteoclast formation. They tried several different treatments, including a chemical compound called DAPT that was particularly effective. DAPT has been shown to help with osteoarthritis by inhibiting function of NOTCH proteins in other studies. Using DAPT as well as Zoledronic acid, a common medication for osteoporosis, “may become a first-line treatment for Hadju-Cheney syndrome,” the researchers conclude in their study.
“By clearly identifying the relationship between FBW7 and NOTCH2 proteins, we have identified potential therapeutic targets for patients with rare bone diseases as well as much more widespread age-related osteoporosis,” said Inuzuka.
Learn more:Â Reversing severe bone loss
The Latest on: Bone loss
[google_news title=”” keyword=”bone loss” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Bone loss
- Bone Broth Drinks Can Heal Your Gut to Boost Weight Loss: Top Doc Shares 3 Recipeson April 25, 2024 at 11:17 am
The same thing has happened to bone broth… the food that is now being lauded as “liquid gold” for its ability to repair a damaged gut, speed weight loss and transform our health. Talk about an unsung ...
- Weight Loss Drugs With Your Gym Membership? What to Knowon April 24, 2024 at 1:22 pm
Weights, aerobics, and … Wegovy? Some in the fitness industry are moving to dispense the popular GLP-1 medications to club members, combining the new, easier method of losing weight with the old, more ...
- Boeing turns lower as 737 Max recovery times cloud earnings updateon April 24, 2024 at 8:33 am
Boeing delivered 83 aircraft to customers over the three months ended in March, the company said, including 67 of its 737 Max jets and 13 of its 787 Dreamliner. The group booked orders for 111 new ...
- After bruising loss, what Willson Contreras does to stay in lineup, to give Cardinals a gripon April 24, 2024 at 5:15 am
Catcher, who is playing with a deep bone bruise and using a bigger mitt to protect his hand, provides one run in ghastly 14-1 loss and then readies to play ...
- This 5-year-old from Gaza is learning to live with one leg and untold losson April 24, 2024 at 3:00 am
In Qatar's capital, a compound housing Palestinian medical evacuees from Gaza is a living catalog of what war does to the human body.
- The 1 Unexpected Side Effect Of Rapid Weight Loss We Don't Talk About Enoughon April 24, 2024 at 12:01 am
The number on the scale is just a number on the scale and is not always worth the stress that comes with weight loss.
- What Makes Bone and Skull Jewelry Popular in 2024?on April 22, 2024 at 1:26 am
Bone and skull jewelry is really cool and famous in 2024. People have cherished this sort of jewelry for a completely long time, from vintage days to now when we like contemporary things. In 2024, ...
- The 10 Healthiest Dairy Foods for Weight Losson April 19, 2024 at 11:33 am
A dietitian shares some of the healthiest dairy products to help with weight loss, like yogurt, fortified milk, and string cheese.
- NIH awards UAMS researchers $2.27 million to study estrogen’s role in preventing bone losson April 13, 2024 at 12:00 am
Researchers at the University of Arkansas for Medical Sciences (UAMS) will use a $2.27 million grant from the National Institutes of Health (NIH) to answer key questions about the cellular ...
via Bing News