Did you know that the same protein that helps your body respond to certain cellular signals also plays a part in bone breakdown? Meet Tumor necrosis factor receptor-associated factor 1, or TRAF1 for short. This little-known player has been found to boost osteoclastogenesis, the process that leads to bone loss. But how does it do this? By tweaking the way cells handle energy, particularly through something called oxidative phosphorylation (OXPHOS).
Imagine TRAF1 as a puzzle piece that fits perfectly during bone loss. Researchers discovered that TRAF1 levels rise sharply during osteoclastogenesis. The more TRAF1 around, the worse osteoporosis gets. When scientists removed TRAF1 from mice, they found something interesting. The bone mass in adults increased, both in normal and ovariectomized mice (mice that had their ovaries removed, leading to bone loss similar to menopause in humans). However, childhood bone mass remained unaffected.
Now, here’s where it gets tricky. TRAF1 also boosts OXPHOS in osteoclasts by bumping up the activity of a protein named AKT. Usually, a protein called TRAF2 would step in to put the brakes on this process. But TRAF1 steps in and stops TRAF2 from carrying out its usual task. This allows AKT to become more active and increases OXPHOS.
When researchers tried to reverse the effects of removing TRAF1 by reintroducing AKT, they found that the bone-boosting effect came back. This shows that TRAF1’s role in bone resorption is strongly tied to AKT. In essence, TRAF1 acts like a helper that assists in bone loss by keeping energy levels up and AKT active.
This discovery gives us a new view into how bones break down. It also suggests that TRAF1 could be a target for treating osteoporosis. By understanding and maybe even manipulating the TRAF1-AKT-OXPHOS axis, we might find new ways to manage bone loss.
