It is still unknown where from osteoblasts are recruited during remodeling of adult human cancellous bone. Still, it is often suggested that they originate from perivascular osteoprogenitors in the bone marrow (BM). Here we propose also the existence of a layer of osteoprogenitors at the periphery of the BM. This proposal is based on electron and light microscopy of the bone surface and of the neighboring BM in human iliac crest biopsies, where we quantified cell densities, cell proliferation, osteoblast differentiation markers, and capillaries (n=14) (Danish Ethical Committee S20070121).
We found that quiescent surfaces are not only covered by bone lining cells, but also by very flat (< 0.1 μm) and elongated cells, which are P3NP-positive and surround the whole BM. At the level of osteoclasts, this cell envelope appears lifted forming a canopy over the remodeling site a view which is supported by the physical continuity between this canopy and the BM envelope at the level of quiescent surfaces, and by the fact that the vast majority of osteoclast surfaces are covered by a canopy. Canopies proved to consist of osteoblast-lineage cells which are more proliferative and less differentiated than bone surface cells, as shown by the inverse levels of Ki-67 and P3NP vs osterix. Furthermore, the presence of capillary-canopy contacts peaked over osteoclast surfaces, and the number of capillary-canopy contacts correlated positively with the osteoblast density on bone-forming surfaces. Interestingly, canopy cell density was negatively affected by age, and correlated also positively with osteoblast density on bone-forming surfaces.
In conclusion, the present data point to the BM envelope as a source of osteoprogenitors. Its dual interaction with osteoclasts and capillaries upon initiation of the bone remodeling cycle fits the current knowledge of the role of osteoclasts and vasculature in triggering osteogenesis.
17 May 2014 - 20 May 2014