During development, bones are reshaped and increase in size in response to mechanical stresses from neighbouring growing organs. Osteoclasts dissolve and resorb old bones, while osteoblasts form new bones. Here, Koichi Matsuo and colleagues examine how osteoblasts and osteoclasts coordinate growth between the outer periosteum and inner endosteum of the mouse fibula. First, from histological analyses, the authors find that osteoclasts and osteoblasts are paired across the periosteal and endosteal surfaces. Micro-CT imaging show that the sites of strong periosteal osteoclast activity correspond to the sites of compression from surrounding muscles. The authors observe mature osteoblasts in the endosteum, while preosteoblasts are found in both the periosteum and cortical canals linking the periosteum and endosteum. X-ray tomographic microscopy show that these cortical canals are associated with the region where periosteal osteoclasts and endocortical osteoblasts are paired. Furthermore, the authors find that nerve injury, which reduces muscle compression, increases periosteum thickness and abolishes directional pairing of periosteal bone resorption and endosteal bone formation. Finally, using lineage-tracing, the authors find that periosteal osteoblast progenitors migrate through cortical canals to become endosteal osteoblasts. Overall, the findings suggest that bone resorption by periosteal osteoclasts paired with bone formation by endosteal osteoblasts, namely ‘endo-forming trans-pairing’, shape the growing bone.
