Involvement of 3D osteoblast migration and bone apatite during in vitro early osteocytogenesis

- We provide evidence for a new pathway for osteocytogenesis via osteoblast migration.
- Bone apatite appears as a stimulus for osteoblast migration inside the matrix and differentiation into early osteocytes.
- We used synthetic bone-like apatite platelets in terms of structure and properties.
- Osteoblasts were cultured on osteoid-like matrices in terms of collagen density, texture and 3D features.
- Our results promise original models to study fundamental questions on biomineralization.

The transition from osteoblast to osteocyte is described to occur through passive entrapment mechanism (self-buried, or embedded by neighboring cells). Here, we provide evidence of a new pathway where osteoblasts are “more” active than generally assumed. We demonstrate that osteoblasts possess the ability to migrate and differentiate into early osteocytes inside dense collagen matrices. This step involves MMP-13 simultaneously with IBSP and DMP1 expression. We also show that osteoblast migration is enhanced by the presence of apatite bone mineral. To reach this conclusion, we used an in vitro hybrid model based on both the structural characteristics of the osteoid tissue (including its density, texture and three-dimensional order), and the use of bone-like apatite. This finding highlights the mutual dynamic influence of osteoblast cell and bone extra cellular matrix. Such interactivity extends the role of physicochemical effects in bone morphogenesis complementing the widely studied molecular signals. This result represents a conceptual advancement in the fundamental understanding of bone formation.