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Modelling Joint Development: Integrating Biological and Mechanical Influences

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Role of force during embryonic joint development

EU-funded researchers have provided experimental evidence for the role of mechanical forces in joint formation during embryonic development. Treatment of osteoporosis and tissue regeneration will benefit from these advances.

Health

Most joints in the human body are synovial joints, the most mobile type of joint that consists of two bones connected in part by a joint cavity containing synovial fluid that acts as a lubricant. During embryonic development, cartilage-making cells (chondrocytes) at the joint site stop dividing and form an ‘interzone’ from which the synovial cavity develops. Upon initiation of cavity formation, the opposing cartilaginous parts gradually form the ends of the two bones to complete formation of the synovial joint. Mechanical forces such as those related to activity enhance bone strength during life and play a role in minimising osteoporosis. Similarly, mechanical forces are required for synovial cavity formation. However, it is as yet unclear if such forces are also required for producing the articular surfaces. In order to address this issue and its important implications for medical application, European researchers initiated the ‘Modelling joint development: Integrating biological and mechanical influences’ (Modelling_JOINT_DEV) project. Scientists opted to pursue experimental rather than computational methods to investigate the initial hypothesis. They chose the embryonic chick hip joint as a model. The synovial hip joint, the largest in the human body, is composed of the thigh bone (femur) and the hip bone. Three-dimensional (3D) images of embryonic chick and mouse hip over a range of normal embryonic development periods were obtained using the open-source Visualization ToolKit (VTK), after which they were imported into the open-source ParaView platform for comparison and selection of representative reference joints. Embryonic chick hips were immobilised every day from the fifth day of incubation using a neuromuscular blocking agent and harvested at days seven, eight and nine. Immobilised embryos demonstrated reduced femoral bone formation and, in some cases, the femoral head was completely undefined. Slicing and staining to identify various relevant tissue types was conducted and relevant analyses have been commenced. Preliminary data suggests that mechanical force may in fact be required not only for joint cavity formation but also for bone formation in embryonic development.

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