Osteoblast-derived osteomodulin restrains osteoclastogenesis via ITGB8/RRM2-mediated reduction of mitochondrial respiration and mitochondrial ATP production - PubMed
a day ago
- #osteoporosis
- #osteoclastogenesis
- #mitochondrial respiration
- Osteomodulin (OMD), derived from osteoblasts, inhibits osteoclast formation by reducing mitochondrial respiration and ATP production.
- OMD levels are lower in postmenopausal osteoporosis patients, suggesting its protective role against excessive bone resorption.
- Mechanistically, OMD interacts with integrin β8, suppresses RhoA activity, and reduces YAP/TEAD-mediated RRM2 transcription, leading to decreased mitochondrial function.
- Recombinant OMD or RRM2 inhibition can mitigate bone loss in models like ovariectomy and lipopolysaccharide-induced osteoporosis.
- The study highlights the OMD-integrin β8-RhoA-YAP/TEAD-RRM2 axis as a key regulator linking extracellular matrix signaling to osteoclast bioenergetics.