Muscle Contraction Is Necessary to Maintain Joint Progenitor Cell Fate

Abstract

During embryogenesis, organ development is dependent upon maintaining appropriate progenitor cell commitment. Synovial joints develop from a pool of progenitor cells that differentiate into various cell types constituting the mature joint. The involvement of the musculature in joint formation has long been recognized. However, the mechanism by which the musculature regulates joint formation has remained elusive. In this study, we demonstrate, utilizing various murine models devoid of limb musculature or its contraction, that the contracting musculature is fundamental in maintaining joint progenitors committed to their fate, a requirement for correct joint cavitation and morphogenesis. Furthermore, contraction-dependent activation of beta-catenin, a key modulator of joint formation, provides a molecular mechanism for this regulation. In conclusion, our findings provide the missing link between progenitor cell fate determination and embryonic movement, two processes shown to be essential for correct organogenesis.

Life in the Slow Lane: The Effect of Reduced Mobility on Tadpole Limb Development

“…Likewise, in murine embryos immobilization does not affect all joints in the same way. Despite immobility, knee and finger joints remain intact in the mutant mice (Kahn et al, 2009). Our results support the current hypothesis that movement plays no role in joint specification (Kahn et al, 2009) because in the digits joints of the experimental tadpoles, the interzone formation was not affected, but joint cavity formation was disrupted.…”

“…Despite immobility, knee and finger joints remain intact in the mutant mice (Kahn et al, 2009). Our results support the current hypothesis that movement plays no role in joint specification (Kahn et al, 2009) because in the digits joints of the experimental tadpoles, the interzone formation was not affected, but joint cavity formation was disrupted. Thus, our data support the findings of other authors indicating that immobilization inhibits joint cavity formation without affecting earlier joint specifications (Pitsillides, 2006).…”

“…The four main effects that are observed in tadpoles can be recognized in amniotes such as birds (chick embryos: Sullivan, 1966;Murray and Drachman, 1969;Hall, 1975;Hall and Herring, 1990;Quin et al, 1998;Pitsillides, 2006), and mammals (rat embryos: Quinn et al, 1998;Coutinho et al, 2002;Kahn, 2009). Based on these data (Fig.…”

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

“…In fact, cells residing in virtually all developing organs, including muscle, 39 brain, 40,41 kidneys, 42,43 and the haematopoietic system, 44,45 are sensitive to exogenous mechanical cues. For example, the heart starts pumping blood in Xenopus embryos using a hydrostatic impedance pumping mechanism in which waves of contraction and elastic deformation of the heart chamber create dynamic suction forces that drive blood flow even before valve formation, 46 and disruption of myosin-based tension generation during the initial stages of heart looping disrupts morphogenesis, 47 demonstrating the important interplay between these exogenous mechanical forces and actomyosin contractility in developing organs.…”

Molecular profiling of synovial joints: Use of microarray analysis to identify factors that direct the development of the knee and elbow

“…The interaction of these signaling pathways appears to be coordinated within the interzone by heparin sulfate proteoglycans to assure proper joint morphogenesis (Mundy et al, 2011). Finally, muscle movement and the biophysical stimuli generated by muscle contractions also play a fundamental role in joint development, critical for cavitation and maintenance of the joint space (Kahn et al, 2009).…”