IADR Abstract Archives
Lrp1 Controls Postnatal Facial Growth
Objectives: The low-density lipoprotein receptor (Ldlr) gene family comprises a group of multifunctional transmembrane proteins that regulate various biological processes including lipoprotein homeostasis, neurodevelopment and bone remodeling. The Ldlr-related proteins (Lrps) Lrp4, Lrp5 and Lrp6 have been shown to participate in craniofacial organogenesis. However, the role of Lrp1 in craniofacial development is unknown.
Methods: Mice lacking Lrp1 specifically in the osteoblast lineage were generated using the cre-loxP system with cre recombinase expression under the control of the Runx2 promoter (Lrp1Runx2 cre) and analysed at 6, 12 and 24 weeks of age by micro-computed tomography scanning, decalcified and undecalcified histology.
Results: Micro-computed tomography scanning revealed a significant reduction of the skull length in Lrp1Runx2 cre mice as compared to wild-type mice at all ages. More specifically, the length of the frontal and nasal bones was significantly reduced in Lrp1Runx2 cre mice, whereas other calvarial bones were unaffected. The impairment of the frontonasal growth was associated with malalignment and overgrowth of the incisor teeth in Lrp1Runx2 cre mice. This prompted us to study bone formation in the frontonasal suture by decalcified and undecalcified histology. These analyses revealed tumor-like proliferation of mesenchymal cells and ectopic intrasutural as well as periostal bone formation in the frontonasal suture of Lrp1Runx2 cre mice. In vivo analysis of bone formation using fluorescent calcein confirmed disorganization of bone apposition in Lrp1Runx2 cre mice and less bone growth at the sutural surfaces as compared to wild-type mice.
Conclusions: Taken together, our analyses demonstrate that Lrp1 controls postnatal facial growth in mice by regulating bone apposition in the frontonasal suture. Mutations in LRP1 should therefore be considered in gene association studies of patients with growth-related jaw discrepancies.
Methods: Mice lacking Lrp1 specifically in the osteoblast lineage were generated using the cre-loxP system with cre recombinase expression under the control of the Runx2 promoter (Lrp1Runx2 cre) and analysed at 6, 12 and 24 weeks of age by micro-computed tomography scanning, decalcified and undecalcified histology.
Results: Micro-computed tomography scanning revealed a significant reduction of the skull length in Lrp1Runx2 cre mice as compared to wild-type mice at all ages. More specifically, the length of the frontal and nasal bones was significantly reduced in Lrp1Runx2 cre mice, whereas other calvarial bones were unaffected. The impairment of the frontonasal growth was associated with malalignment and overgrowth of the incisor teeth in Lrp1Runx2 cre mice. This prompted us to study bone formation in the frontonasal suture by decalcified and undecalcified histology. These analyses revealed tumor-like proliferation of mesenchymal cells and ectopic intrasutural as well as periostal bone formation in the frontonasal suture of Lrp1Runx2 cre mice. In vivo analysis of bone formation using fluorescent calcein confirmed disorganization of bone apposition in Lrp1Runx2 cre mice and less bone growth at the sutural surfaces as compared to wild-type mice.
Conclusions: Taken together, our analyses demonstrate that Lrp1 controls postnatal facial growth in mice by regulating bone apposition in the frontonasal suture. Mutations in LRP1 should therefore be considered in gene association studies of patients with growth-related jaw discrepancies.