Mechanobiology of embryonic skeletal development: Insights from animal models

Abstract

A range of clinical conditions in which fetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, particularly the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, whereas genetically modified mice with nonfunctional or absent skeletal muscle offer a valuable tool for examining the interplay between muscle forces and skeletogenesis in mammals. This article reviews the body of research on animal models of bone or joint formation in vivo in the presence of an altered or abnormal mechanical environment. In both immobilized chicks and "muscleless limb" mice, a range of effects are seen, such as shorter rudiments with less bone formation, changes in rudiment and joint shape, and abnormal joint cavitation. However, although all bones and synovial joints are affected in immobilized chicks, some rudiments and joints are unaffected in muscleless mice. We propose that extrinsic mechanical forces from movements of the mother or littermates impact on skeletogenesis in mammals, whereas the chick embryo is reliant on intrinsic movement for mechanical stimulation. The insights gained from animal models into the mechanobiology of embryonic skeletal development could provide valuable cues to prospective tissue engineers of cartilage and bone and contribute to new or improved treatments to minimize the impact on skeletal development of reduced movement in utero.

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures

“…There is evidence that application of mechanical stimuli can determine the developmental fate of mesenchymal stem cells (MSCs) [6]. In particular, appropriate physical stimuli are reported to be essential for limb development: synovial joint and articular cartilage formation in chicken and murine embryos require proper mechanical forces by muscle contractions [7,8]. Optimal intermittent biomechanical activation is also essential for cartilage regeneration during osteoarthritis (reviewed by Sun [9]).…”

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

“…Chondrocytes are also challenged by osmotic and hypoxic stress under physiological circumstances [65]. Whilst optimal mechanical stimulation is necessary for cartilage development [66] and homeostasis, extreme levels of loading have also been shown to initiate cartilage degradation [65]. A recent publication reported that in ovo immobilization of chicken embryos resulted in fused articular surfaces in the knee joint [67].…”

Signaux moléculaires et mécaniques intervenant dans la différenciation des cellules tendineuses

“…La mécanobiologie du tendon a été étudiée in vivo au cours du développement. Une paralysie des embryons de poulet au stade E7.5 a été induite par traitement au bromure de décaméthonium (DMB), un agoniste du récepteur à l'acétylcholine bloquant la jonction neuromusculaire [7]. Le traitement au DMB va induire une paralysie musculaire et donc interrompre les mouvements rythmiques effectués par l'embryon ( Figure 1A).…”