Journal
CELL AND TISSUE RESEARCH
Volume 383, Issue 3, Pages 1135-1153Publisher
SPRINGER
DOI: 10.1007/s00441-020-03300-y
Keywords
Collagen; Integrin; Cell adhesion; Bone homeostasis; ECM receptors
Categories
Funding
- University of Oulu
- Finnish Centre of Excellence Programme of the Academy of Finland [251314, 294617, 308867, 268378, 273571]
- Sigrid Juselius Foundation
- Centre for Cancer Biomarkers (Centre of Excellence - Research council of Norway) [223250]
- Norwegian Centre for International Cooperation in Education [Diku: NNA-2016/10026]
- European Research Council under the European Union [336267]
- European Commission Regional Development Fund [538/2010]
- Oulu University Hospital
- Academy of Finland (AKA) [308867, 294617] Funding Source: Academy of Finland (AKA)
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Collagen XIII is a transmembrane collagen expressed in mesenchymal tissues, and it interacts with integrin alpha 11 beta 1 to regulate bone homeostasis. The study showed that integrin alpha 11 beta 1 acts as a receptor for collagen XIII, mediating cell adhesion to specific collagenous motifs, and plays a role in maintaining bone homeostasis.
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 alpha 11 beta 1 is a collagen receptor known to recognize the GFOGER (O=hydroxyproline) sequence in collagens. Interestingly, collagen XIII and integrin alpha 11 beta 1 both have a role in the regulation of bone homeostasis. To study whether alpha 11 beta 1 is a receptor for collagen XIII, we utilized C2C12 cells transfected to express alpha 11 beta 1 as their only collagen receptor. The interaction between collagen XIII and integrin alpha 11 beta 1 was also confirmed by surface plasmon resonance and pull-down assays. We discovered that integrin alpha 11 beta 1 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 alpha 11-I domain. Furthermore, we studied the in vivo significance of the alpha 11 beta 1-collagen XIII interaction by crossbreeding alpha 11 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 alpha 11 beta 1 as a new collagen XIII receptor and demonstrates that this ligand-receptor pair has a role in the maintenance of bone homeostasis.
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