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| Item Type: | Article |
|---|---|
| Title: | Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth |
| Creators Name: | Dzamukova, M., Brunner, T.M., Miotla-Zarebska, J., Heinrich, F., Brylka, L., Mashreghi, M.F., Kusumbe, A., Kühn, R., Schinke, T., Vincent, T.L.. and Löhning, M. |
| Abstract: | Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined. Here we show that mechanical forces, associated with increased body weight at the end of adolescence, trigger the mechanoreceptor PIEZO1 and thereby mediate enhanced production of the kinase FAM20C in osteoblasts. FAM20C, the major kinase of the secreted phosphoproteome, phosphorylates dentin matrix protein 1, previously identified as a key factor in bone mineralization. Thereupon, dentin matrix protein 1 is secreted from osteoblasts in a burst-like manner. Extracellular dentin matrix protein 1 inhibits vascular endothelial growth factor signalling by preventing phosphorylation of vascular endothelial growth factor receptor 2. Hence, secreted dentin matrix protein 1 transforms type H vessels into type L to limit bone growth activity and enhance bone mineralization. The discovered mechanism may suggest new options for the treatment of diseases characterised by aberrant activity of bone and vessels such as osteoarthritis, osteoporosis and osteosarcoma. |
| Keywords: | Bone Development, Bone Matrix, Calcinosis, Ion Channels, Morphogenesis, Physiologic Calcification, Vascular Endothelial Growth Factor A |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 3059 |
| Date: | 1 June 2022 |
| Official Publication: | https://doi.org/10.1038/s41467-022-30618-8 |
| PubMed: | View item in PubMed |
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