Loss of essential enzymatic processes can increase the risk of bone fractures

Loss of enzymatic processes within the body can reduce a person’s risk of fracture from bone. This new view was published in eLife by an international team of scientists and engineers led by Deepak Vashishth, director of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at the Rensselaer Polytechnic Institute.

Enzymatic processes are essential for any number of chemical reactions that occur within the body, including the production of the extracellular matrix within bone that is essential for mechanical support. Phosphorylation – one of these key enzymatic processes – is phosphoryl binding to proteins, and is essential for cell regulation. This process has a place in many diseases, but until now, researchers did not know whether it altered the integrity of tissue and organ function.

In this paper, researchers looked at a protein called osteopontin, which plays a vital role in holding the matrix together. The researchers developed a process by which they could stimulate phosphorylation – or its counterpart, dephosphorylation – in bones from genetically modified mice, some with osteopontin and some without.

By comparing results from the two groups, researchers found that fracture hardness, a measure of bone mechanical strength, increased with osteopontin phosphorylation and decreased with dephosphorylation. In particular, phosphorylation improved crosslinks and increased the attraction between the charged groups of osteopontin and bone mineral, making bone stronger and fracture more difficult.

This is the first study to rule out that phosphorylation in bone cases, especially as it helps bone to release energy, and that the loss of this change is bad for bone . “

Deepak Vashishth, Director, Center for Biotechnology and Interdisciplinary Studies (CBIS), Rensselaer Polytechnic Institute

The team also studied the effect of osteopontin phosphorylation levels in the rare bone diseases hypophosphatemia and hyperphosphatemia, which are associated with skeletal deformities. In both diseases, Vashishth said, osteopontin phosphorylation levels decreased, a finding that bears the groundwork for further study.

“Another promising finding is that these levels change with bone diseases,” Vashishth said. “Does phosphorylation directly affect bone bias in these sick conditions? And what therapeutic tools can we use to resolve this? These are the questions we want to study.”

In the spirit of New Polytechnic, Rensselaer’s leading research and education model, this research was highly collaborative across multiple disciplines. Vashishth and his laboratory worked with researchers at McGill University in Canada, the University of Southampton in the United Kingdom, the University of Patras in Greece, the University of Aarhus in Denmark, and the Vienna University of Technology in Austria. Each research team brought a different experience and piece of this puzzle to work.

The team’s findings can be applied to similar processes within other connective tissue and therapeutics that may counteract infectious osteopontin phosphorylation levels.

“This isn’t just specific to bone, because phosphorylation is a more ubiquitous change in other cigarettes in the body,” Vashishth said. “Osteopontin is not just in bone, it’s in other cigarettes in our body, like our kidneys and several other places. This research can shed light on other things that can happen throughout the body. “