Figure 1

Bone repair of the cortical tibia injury in Nf1Prx1 mice is accelerated by systemic high-dose lovastatin treatment. (A)-(C') Masson-Goldner stained transverse paraffin sections of the drill channel (white dotted lines) 7 days post injury. (A), (A') New bone is formed in the marrow cavity in control animals (arrow). (A') The presence of cartilage suggests that cortical repair relies at least partially on endochondral bone formation (star). Recruited mesenchymal cells differentiate into osteoblasts embedded in the collagenous (green/blue) extracellular matrix (arrows). (B), (B') In mutant animals the entire cortical bone surrounding the injury site appears unmineralised as indicated by the orange stained matrix (arrow). Recruited fibroblasts fail to differentiate and collagenous matrix (see the green coloured matrix in (A')) is not produced. Formation of new bone in the bone marrow cavity is delayed, indicating a failure of repair process initiation. The cartilage is formed excessively (star) and the entire injury site is filled with fibro-cartilaginous tissue (f). (C), (C') Lovastatin treatment normalises the cortical bone quality around the injury site (note absence of orange staining). Recruited mesenchymal progenitor cells deposit green stained collagenous matrix (arrows). New bone is formed in the marrow cavity (arrow) as well as in the cortical region (nb). (D)-(F') Masson-Goldner staining of transverse sections of the injury site 14 days post induction. (D)-(E') Trabecular bone is present in the marrow space in control as well as in mutant animals (arrows). (E), (E') Nf1Prx1 mice exhibit persistence of fibrous (f) and cartilaginous (star) tissue in the area of the injury site. Reduced mineralisation is indicated by orange structures (arrow). (F), (F') No fibro-cartilaginous tissue is detected in the lovastatin-treated group. The cortical bone (c) in lovastatin-treated mice appears thicker and no signs of demineralisation are found; (m) denotes muscle.