Penn Dental Medicine Study Identifies Possible Target to Counter Bone Loss

PHILADELPHIA, Oct. 12, 2022 /PRNewswire/ — Bone remodeling in the body involves a balancing act between osteoblasts, cells that build bone, and osteoclasts, cells that break it down. Diseases such as osteoporosis, arthritis, and periodontitis involve bone loss, and are linked with an overabundance of osteoclast activity.

In a paper published in Proceedings of the National Academy of Sciences, researchers at the University of Pennsylvania School of Dental Medicine and colleagues offer new insights into the regulation of osteoclasts, potentially shedding light on the imbalances that can cause osteolytic diseases. The work identifies the protein IFT80 as a key player in keeping populations of osteoclasts in check. The team found that mice lacking IFT80 grew larger-than-expected populations of osteoclasts, and subsequently developed severe osteopenia.

“When you think about translation to the clinic, we believe this finding is very important,” says Shuying (Sheri) Yang, an associate professor at Penn Dental Medicine and the study’s senior author. “As we begin to understand the mechanism and the gene function of IFT80, we may be able to consider it and its downstream proteins as potential therapeutic targets.”

Yang became interested in studying the role of IFT80 in hematopoietic stem cell lineage after an earlier study in Nature Cell Biology. It revealed that IFT, or intraflagellar proteins, play a role in transporting proteins of T cells. These proteins are a focus of Yang’s lab, and the finding piqued her interest as T cells and osteoclasts are both derived from hematopoietic stem cells, the precursors of blood cells. IFTs help construct cilia, antenna-like sensory organelle that extend from cells, by transporting proteins from the cilia’s base to their tip and back again. In previous work, Yang and others had shown that IFTs play critical roles in regulating osteoblasts and chondrocytes, from mesenchymal stem cells, which make and maintain bone and cartilage.

This recent study is the first to link IFT80 with a role in osteoclasts and to find that IFT80 controls a protein degradation pathway and serves as a negative regulator during osteoclast differentiation. These features makes it a valuable target for potential therapeutic intervention, says Yang.

“With so many diseases related to excess bone loss, there is a big need to find ways to address bone loss and restore balance in bone remodeling,” adds Yang. Read more >

Media contact: Beth Adams, [email protected]

SOURCE Penn Dental Medicine

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