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INFLUENCE OF JOINT MOVEMENT ON IN VIVO REGENERATION OF SKELETAL TISSUE: DIFFERENTIATION SIGNAL TRIGGERED BY JOINT MOVEMENT



Abstract

Purpose: The deleterious effects of blocking movement of normal joints has been demonstrated by numerous animal experiments and clinical observations. Conversely, mobilisation of the joints leads to metabolic and trophic effects commonly attributed to changes in the nutritional status of the cartilage. In vitro experiments and mechanobiological studies have however suggested that more fundamental mechanisms are operating, demonstrating the impact of physical factors on biological cell regulation and tissue organisation. The purpose of our experimentation was to study the biological effects of movement on a model of skeletal regeneration from mesenchymatous tissue. The tested hypothesis was that movement crossing a living tissue causes the emission of specific signals which contribute to its anatomic and functional organisation.

Material and methods: We used 27 immature rabbits for the model. We transferred a vascularised periosteal flap to the knee region in order to initiate a process of skeletal tissue regeneration. The regenerated tissue was submitted to joint movements caused by the animal’s spontaneous movements. In the first group of animals, the knee was left intact. In the second group, 25 mm of the distal femur was removed, including the condyles. Tissue regeneration was compared with that obtained without joint movement.

Results: Qualitative changes in regenerated tissue were found to be influenced by movement. The differentiation of the mesenchymatous precursors was oriented towards production of cartilage and fibrocartilage. In the group with a sectioned femur, a mobile cartilage joint space was obtained at the interface between the regenerated femur and the tibia. A functional neo-joint was formed.

Discussion: This model of tissue regeneration, similar to that observed in experimental nonunion, demonstrated the contribution of multipotent stem cells of diverse origins. Joint mobility and its mechanical consequences produced information which were perceived as a modification of the environment. They regulated the differentiation of pluripotent cell elements and thus guided the spatial and temporal organisation of in vivo tissue repair processes.

Conclusion: Our results confirm the major influence of mechanical constraints on the organisation of skeletal tissue. The effect is expressed by the remodelling of mature tissues, but is also observed in immature tissues implicated in morphogenesis and skeletal regeneration processes. The transduction mechanisms remain to be described. However, the results obtained for cartilage regeneration demonstrate the practical interest of periosteal arthroplasty. Further improvement of the model to optimise continuous passive movement would open new perspectives for in vivo joint regeneration.

Correspondence should be addressed to SOFCOT, 56 rue Boissonade, 75014 Paris, France.