PNAS scientists have discovered a new function of a protein – fighting bone loss

The researchers discovered a new function of a protein that regulates osteoclasts (the cells that break down bone), which could pave the way
for the invention of new therapies to prevent bone loss.

Bone remodeling in the human body is a delicate balance
between osteoblasts (the cells that make bones) and osteoclasts (the cells that break down bones).

Researchers at the University of Pennsylvania and their colleagues, in a recent study published in the journal Proceedings of the National Academy of Sciences, offer new insights into the regulation of osteoclasts, potentially revealing imbalances
that can lead to disease.

Shuying (Sheri) Yang, associate professor at the University of Pennsylvania School of Dentistry and senior author of the study, said: "We think this finding is very important
when you think about translating it into the clinic.

After seeing an earlier study in Natural Cell Biology, Yang and his colleagues became interested in
IFT80.

IFTs aid the formation of cilia by transporting proteins from the base of the cilia to the tip of the cilia and back again, which are the antennae-like sensory organs
that extend out of the cell.

To explore the role of IFT80 in osteoclasts, Yang's team developed a knockout mouse line that lacked proteins
in osteoclast precursors.

Further experiments showed that IFT80 interacts with a protein called Cbl-b in the protein degradation pathway regulated by the small regulatory protein ubiquitin in osteocles
.

To verify whether IFT80 can be a potential target for intervention in bone loss disease, the researchers overexpressed IFT80
in a mouse model that typically experiences bone loss caused by osteoclast overactivity.

The study first linked IFT80 to the role of osteoclasts and found that IFT80 controls a protein degradation pathway that acts as a negative regulator during osteoclast differentiation
.

“IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation” by Vishwa Deepak, Shu-ting Yang, Ziqing Li, Xinhua Li, Andrew Ng, Ding Xu, Yi-Ping Li, Merry Jo Oursler and Shuying Yang, 21 June 2022, Proceedings of the National Academy of Sciences.

“Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse” by Francesca Finetti, Silvia Rossi Paccani, Maria Giovanna Riparbelli, Emiliana Giacomello, Giuseppe Perinetti, Gregory J.
Pazour, Joel L.
Rosenbaum, and Cosima T.
Baldari, 25 October 2009, Nature Cell Biology.