New discovery provides insight into bone loss diseases  

New discovery provides insight into bone loss diseases  
© iStock/fizkes

Enhanced treatment for bone loss diseases could be on the horizon as researchers reveal novel insight into osteoclasts.

A research team at the University of Pennsylvania has uncovered new insights into the regulation of osteoclasts – the cells which break down bones – potentially unearthing vital information about the imbalances that cause bone loss diseases.

The work identifies the protein IFT80 as a critical player in managing populations of osteoclasts. In mice lacking in IFT80, they grew larger-than-expected osteoclasts populations resulting in the bone loss disease called osteopenia.

The findings are published in Proceedings of the National Academy of Sciences journal.

Researching IFT80 and its important role

In an earlier study, Shuying (Sheri) Yang, an Associate Professor in Penn’s School of Dental Medicine and the study’s senior author and his colleagues first became interested in the role of IFT80 and its role in T cell protein transport.

Following this discovery, the researchers explored IFT80 in osteoclasts. The research team developed a knockout mouse line that lacked the protein in precursors of osteoclasts. They discovered a significantly lower bone volume compared to normal mice, and their osteoclasts nearly doubled in number, potentially causing bone loss diseases.

The researchers discovered that IFT80 prevents osteoclast precursors from giving rise to bone-resorbing cells and inhibits osteoclast maturation.

Moreover, researchers experimented further and discovered that IFT80 interacted with a protein called Cbl-b in the protein degradation pathway regulated by the small regulatory protein ubiquitin in osteoclasts. Yang’s team revealed that IFT80 prevents the breakdown of Cbl-b, and Cbl-b normally degrades another protein called TRAF6. TRAF6 typically promotes osteoclast production, so by degrading TRAF6, IFT80 inhibits osteoclast differentiation.

The team also found evidence that IFT80 suppresses a signalling pathway governed by the proteins RANKL and RANK.

Potential therapy for bone loss diseases

The team tested whether IFT80 could be a potential target for intervention in bone loss diseases and found overexpressed IFT10 in a mouse model that experienced overactive osteoclasts, which causes bone loss diseases. By doing this, the researchers reduced RANK/RANKL activation, lowered osteoclast production, and increased bone volume in mice.

The study is the first to link IFT80, osteoclasts and bone loss diseases. Additionally, the researchers are the first to discover that IFT80 controls a protein degradation pathway and serves as a negative regulator during osteoclast differentiation.

“Right now there is a lot of interest in how the body promotes osteoclast differentiation,” Yang said. “With so many diseases related to excess loss of bones—osteoporosis, periodontitis, rheumatoid arthritis, even fractures—there is a big need to find ways to address bone loss and restore balance in bone remodelling.”



Please enter your comment!
Please enter your name here