First Author | Koivunen J | Year | 2021 |
Journal | Cell Tissue Res | Volume | 383 |
Issue | 3 | Pages | 1135-1153 |
PubMed ID | 33306155 | Mgi Jnum | J:332766 |
Mgi Id | MGI:7429051 | Doi | 10.1007/s00441-020-03300-y |
Citation | Koivunen J, et al. (2021) Integrin alpha11beta1 is a receptor for collagen XIII. Cell Tissue Res 383(3):1135-1153 |
abstractText | Collagen XIII is a conserved transmembrane collagen mainly expressed in mesenchymal tissues. Previously, we have shown that collagen XIII modulates tissue development and homeostasis. Integrins are a family of receptors that mediate signals from the environment into the cells and vice versa. Integrin alpha11beta1 is a collagen receptor known to recognize the GFOGER (O=hydroxyproline) sequence in collagens. Interestingly, collagen XIII and integrin alpha11beta1 both have a role in the regulation of bone homeostasis. To study whether alpha11beta1 is a receptor for collagen XIII, we utilized C2C12 cells transfected to express alpha11beta1 as their only collagen receptor. The interaction between collagen XIII and integrin alpha11beta1 was also confirmed by surface plasmon resonance and pull-down assays. We discovered that integrin alpha11beta1 mediates cell adhesion to two collagenous motifs, namely GPKGER and GF(S)QGEK, that were shown to act as the recognition sites for the integrin alpha11-I domain. Furthermore, we studied the in vivo significance of the alpha11beta1-collagen XIII interaction by crossbreeding alpha11 null mice (Itga11(-/-)) with mice overexpressing Col13a1 (Col13a1(oe)). When we evaluated the bone morphology by microcomputed tomography, Col13a1(oe) mice had a drastic bone overgrowth followed by severe osteoporosis, whereas the double mutant mouse line showed a much milder bone phenotype. To conclude, our data identifies integrin alpha11beta1 as a new collagen XIII receptor and demonstrates that this ligand-receptor pair has a role in the maintenance of bone homeostasis. |