Fig. 8.

Model of osteocytic EphrinB2 regulation of bone matrix composition. a In control bone (Dmp1Cre) both osteoblasts and osteocytes express EphrinB2. Osteoblasts reside on the bone surface, and pass through a transition (dashed arrows) to become mature, matrix-embedded osteocytes. Osteoblasts deposit collagen-containing osteoid (triple helical collagen fibers, shown on the right). In region 1 of newly formed bone, mineral deposition is initiated. Mineral crystals (black stars) and carbonate (orange circles) continue to accumulate, and collagen fibers become more compact as the matrix matures in regions 2 and 3. b Dmp1Cre.Efnb2^f/f mice express EphrinB2 in osteoblasts, but not osteocytes. Dmp1Cre.Efnb2^f/f osteocytes have increased autophagy (green cells). Osteoid deposition occurs normally, and the initiation of mineralization commences at the same rate, leading to osteoid of the same thickness (red double-headed arrow). As soon as mineralization starts, mineral is deposited in Dmp1Cre.Efnb2^f/f bone at a greater level than control in regions 1, 2, and 3 to reach a level with more mineral, more carbonate substitution, and more compact collagen fibers than controls. Ultimately this leads to more brittle bone. c Close-up of the cell membrane in osteocytes in control and Dmp1Cre.Efnb2^f/f bone: we propose that, in control mice, EphrinB2 suppresses autophagic processes and limits matrix vesicle release via RhoA-ROCK signalling. In Dmp1Cre.Efnb2^f/f mice loss of this inhibition leads to a high level of matrix vesicle release, elevated mineralization, and a brittle bone matrix