The Tfr2 Iron regulator controls bone mass and can be a promising option for excessive bone formation disorders

It is well known that Iron is fundamental for the red blood cells production, bacterial defense and for the correct functioning of all cells present in our body. In particular, the bone tissue is very susceptible to changes in iron metabolism, in fact patients that suffer from iron accumulation (overload) diseases, such as hereditary haemocromatosis, develop premature osteoporosis. Transferrin receptor 2 (Tfr2) is a protein that regulates iron functions and, more interestingly, it is able to interact with the Bone Morphogentic Protein (BMP) that has a critical role in bone metabolism. Based on this, in a recently published work in Nature Metabolism, Martina Rauner, Ulrike Baschant, members of the ECTS Academy, and their colleagues hypothesized that Tfr2 can regulate bone tissue. They found that, in experimental models, the lack of Trf2 caused high bone mass and mineralization, mainly due to the increase of the activity of the osteoblasts, the bone producing cells. This occurred because Trf2 attenuates BMP molecular functions and, concomitantly, reduced the production of inhibitor molecules of the Wnt cellular signaling, a master regulator process for osteoblastic bone formation. Thus, the authors identified  a novel role of Trf2 in bone metabolism. When they re-activated the BMP or the Wnt inhibitors, they rescued the skeletal abnormalities in vivo restoring  osteoblast functionality. More importantly, in light of what discovered, they used the BMP-neutralizing capacity of Trf2 to treat disease models of excessive bone formation due to BMP dysregulation (such as Fibrodysplasia ossificans progressiva, FOP): Trf2 was successfully able to limit bone formation, directly acting on BMP. These important results suggest that Trf2 can be considered a promising therapeutic option to treat heterotopic ossification, a serious and common medical complication after blast injuries or in patients undergoing hip replacement surgery.

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