Introduction: Periosteum osteogenic and chondrogenic properties stimulate the proliferation then differentiation of mesenchymal precursor cells originating from its deeper layers and from neighboring host tissues. The local mechanical environment plays a role in regulating this differentiation of cells into lineages involved in the skeletal regeneration process. Hypothesis: The aim of this experimental animal study is to explore the influence of cyclic high amplitude bending-loading on skeletal tissue regeneration. The hypothesis is that this mechanical loading modality can orient the skeletogenesis process towards the development of anatomical and histological articular structures. Material and methods: A vascularised periosteal flap was transferred in close proximity to each knee joint line in 17 rabbits. On one side, the tibiofemoral joint space was bridged and loading occurred when the animal bent its knee during spontaneous locomotion. On the other side, the flap was placed 12 mm distal to the joint line producing no loading during bending. Tissue regeneration was chronologically analyzed on histologic samples taken from the 4th day to the 6th month. Results: The structure and mechanical behavior of regenerating tissue evolved over time. As a result of the cyclic bending-loading regimen, cartilage tissue was maintained in specific areas of the regenerating tissue. When loading was discontinued, final osteogenic and fibrogenic differentiation occurred in the neoformed cartilage. Fissures developed in the cartilage aggregates resulting in pseudo-gaps suggesting similar processes to embryonic articular development. Ongoing mesenchymal stem cells stimulation was identified in the host tissues contiguous to the periosteal transfer. Discussion: These results suggest that the pseudarthrosis concept should be reconsidered within the context of motion induced articular histogenesis. (C) 2010 Elsevier Masson SAS. All rights reserved.