The DDP3 protein regulates bone mass and might be an important marker for bone diseases such as osteoporosis
When subjected to oxidative stress – a condition in which excess free radicals and reactive metabolites (the so-called reactive oxygen species (ROS)) accumulate in the cell – bone cells can be damaged leading to an increased bone fragility. Therefore, cells possess so-called “anti-oxidant” pathways which allow them to clear or reduce accumulation of these toxic ROS. One of those anti-oxidant pathways is the keap1/Nrf2 (kelch-like ECH associated protein 1/nuclear factor E2-related factor 2) pathway. The roles of antioxidant pathways in bone metabolism and diseases are of great interest. Particularly the role of DDP3, a protein which has been shown in other fields such as cardiology and oncology to serve as an activator of the antioxidant keap1/Nrf2 pathway, has not been studied yet.
In the work published in Journal of Bone and Mineral Research, ECTS Academy member Ciro Menale and colleagues hypothesized that DDP3 is expressed in bone and can regulate bone tissue. They found in experimental models that the lack of DPP3 in bone tissue caused a reduction in bone mass and mineralization which was mainly due to an increased resorptive activity of osteoclasts, the bone resorbing cells, and a decreased activity of osteoblasts, the bone producing cells. This occurred because the absence of DDP3 impaired the Nrf2 antioxidative pathway and thus resulted in increased oxidative stress, and also promoted a pro-inflammatory bone microenvironment which facilitates osteoclast formation and bone resorption. More importantly, looking at the role of DPP3 in bone diseases, they found that DPP3 was significantly reduced in osteoporosis models and that the lack of DDP3 enhanced the bone loss phenomenon.
Overall, the authors demonstrated for the first time that DPP3 plays an important role in maintaining bone mass and the balance between bone formation and bone resorption, and that this molecule is involved in osteoporosis. The results pave the way for further examining DPP3 in osteoporotic patients where DPP3 might represent a novel marker of bone loss.
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