Researchers give more insight into bone diseases

Researchers give more insight into bone diseases
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Tokyo, Japan: Diseases affecting the bones and joints are becoming more widespread in today's elderly populations. For example, in Japan alone, approximately 12 million people suffer from osteoporosis, a disorder that significantly weakens and fragilizes bones. Understanding the biological processes involved in the maintenance of bone and joint tissue is an important first step toward developing effective therapies for these illnesses.

Osteoclasts are a type of cell that plays a crucial role in bone maintenance. These cells absorb and breakdown old or broken bone, letting the body to reuse key elements such as calcium and creating space for new bones. As one may assume, many bone diseases develop when osteoclasts do not perform their functions adequately. Scientists are exploring the processes that control the proliferation and differentiation of precursor cells into osteoclasts.

Interestingly, in a study published in 2020, researchers from Tokyo University of Science (TUS) led by Professor Tadayoshi Hayata revealed that the cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) protein is essential in osteoclast differentiation. They also discovered that this protein, which regulates the stability and translation of messenger RNA (mRNA) molecules, transported into specific structures within the nucleus of the cell when osteoclast differentiation was induced. However, just how this relocation occurs and what Cpeb4 exactly does within these nuclear structures still remains a mystery.

Now, in a recent study published in the Journal of Cellular Physiology on 29 January 2024, Prof. Hayata and Mr. Yasuhiro Arasaki from TUS tackled these knowledge gaps. Motivated by the intricate and complex process of osteoclast differentiation, they sought to more thoroughly understand how the "life cycle" of mRNA, i.e., mRNA metabolism, is involved.

First, the researchers introduced strategic modifications into Cpeb4 proteins and performed a series of experiments in cell cultures. They found that the localization of Cpbe4 in the abovementioned nuclear bodies occurred owing to its ability to bind to RNA molecules. Afterwards, seeking to understand the role of Cpeb4 in the nucleus, the researchers demonstrated that Cpeb4 co-localized with certain mRNA splicing factors. These proteins are involved in the process of mRNA splicing, which is a key step in mRNA metabolism. Put simply, it enables a cell to produce diverse mature mRNA molecules (and eventually proteins) from a single gene.

Through RNA sequencing and gene analysis in Cpeb4-depleted cells, they found that Cpeb4 alters the expression of multiple genes associated with splicing events in freshly differentiated osteoclasts. Finally, through further experiments, the researchers revealed that Cpeb4 only altered the splicing patterns of Id2 mRNA, an important protein known to regulate osteoclast differentiation and development.