Cellular Processes by Which Osteoblasts and Osteocytes Control Bone Mineral Deposition and Maturation Revealed by...

We outline the diverse processes contributing to bone mineralization and bone matrix maturation by describing two mouse models with bone strength defects caused by restricted deletion of the receptor tyrosine kinase ligand EphrinB2.

Stage-specific EphrinB2 deletion differs in its effects on skeletal strength. Early-stage deletion in osteoblasts leads to osteoblast apoptosis, delayed initiation of mineralization, and increased bone flexibility. Deletion later in the lineage targeted to osteocytes leads to a brittle bone phenotype and increased osteocyte autophagy. In these latter mice, although mineralization is initiated normally, all processes involved in matrix maturation, including mineral accrual, carbonate substitution, and collagen compaction, progress more rapidly. Osteoblasts and osteocytes control the many processes involved in bone mineralization; defining the contributing signaling activities may lead to new ways to understand and treat human skeletal fragilities.