New insights into the process of osteogenesis of anosteocytic bone.

The bone material of almost all vertebrates contains the same cellular components. These comprise osteoblasts that produce bone, osteoclasts that resorb bone and osteocytes, which are the master regulators of bone metabolism, particularly bone modeling and remodeling. It is thus surprising that the largest group of extant vertebrates, neoteleost fish, lacks osteocytes entirely (anosteocytic bone). Osteocytes are the progeny of osteoblasts, which become entrapped in the osteoid they secrete, then undergo several morphologic and functional changes, to finally form an intricate network of living cells in the bone matrix. While the process of osteogenesis of osteocytic bone has been thoroughly studied, osteogenesis of anosteocytic bone is less well understood. The current paradigm for formation of anosteocytic bone suggests that osteoblasts remain always on the external surface of the formed bone, and do not become entrapped in the osteoid. Such a process requires the osteoblasts to function in a fundamentally-different way from osteoblasts of all other bony vertebrates. Here we present a comparative structural study of the osteocytic bones of zebrafish and anosteocytic bones of medaka and show that they are remarkably similar in structure at several hierarchical levels. Scanning electron microscopy and phase contrast-enhanced μCT reveal the presence of numerous mineralized objects in the matrix of anosteocytic bone. These objects resemble osteocytic lacunae in zebrafish bone, and their locations and distribution are similar to those of osteocytes in zebrafish bone. Our findings provide support for the occurrence of a process of anosteocytic bone osteogenesis that has so far been rejected. In this process osteoblasts become entrapped in the bone matrix (as occurs in osteogenesis of osteocytic bone), but then undergo apoptosis, become mineralized and end up as part of the mineralized bone matrix.