Bone Abstracts

Differentiation of osteoclast progenitor cells into mononucleated TRAcP+ pre-osteoclasts occurs in the bone marrow. But how are these cells dispatched to the future bone resorption sites? We hypothesized that the collagen type III/I-rich reticulin network of the bone marrow might provide a structural framework for localization and migration of differentiating pre-osteoclasts towards the bone surface. Therefore, adjacent sections from decalcified paraffin-embedded iliac crest biopsies from 11 human controls were either stained for reticular fibers, or double-/triple-immunostained for collagens and cell markers. The association between mononuclear cells positive for osteoclast markers and capillaries or collagen fibers was quantified through histomorphometry, and further analyzed by 3D-reconstructions. Numerous mononuclear TRAcP+ cells were identified within the bone marrow. These cells stained also for other osteoclast markers such as OSCAR and cathepsin K, demonstrating that they are pre-osteoclasts. Staining for reticulin, collagen type I, III, and CD34, combined with 3D-reconstructions, revealed collagen III/I-rich reticulin fibers forming a network throughout the bone marrow. These fibers were connected to the blood vessel network and to bone remodeling compartment canopies, forming a continuum with the collagen present in these structures. Interestingly, double-immunostainings revealed that 93% of the TRAcP+ or OSCAR+ pre-osteoclasts were associated with these collagen fibers and with the collagen of the vascular wall. In conclusion, the close association of pre-osteoclasts with the collagen III/I-rich reticulin and blood vessel networks supports the hypothesis that these linear structures provide a physical support for trafficking of differentiating pre-osteoclast towards the bone remodeling compartment canopies covering resorptive surfaces.