The effect of growth-mimicking continuous strain on the early stages of skeletal development in micromass culture.
Embryonic skeletogenesis involves proliferation, condensation and subsequent chondrogenic differentiation of mesenchymal precursor cells, and the strains and stresses inherent to these processes have been hypothesized to influence skeletal development. The aim of this study was to determine the effect of growth-mimicking strain on the process of early skeletal development in vitro. To this end, we applied continuous uniaxial strain to embryonic skeletal precursor cells in micromass culture. Strain was applied at different times of culture to specifically address the effect of mechanical loading on the sequential stages of cellular proliferation, condensation and differentiation. We found that growth-mimicking strain at all three times did not affect proliferation or chondrogenic differentiation under the tested conditions. However, the timing of the applied strain did play a role in the density of mesenchymal condensations. This finding suggests that a mechanically dynamic environment, and specifically strain, can influence skeletal patterning. The growth-mimicking micromass model presented here may be a useful tool for further studies into the role of mechanical loading in early skeletal development.
School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, Massachusetts, 02138, United States of America; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, Massachusetts 02115, United States of America; Dept. Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Darinka D
DD
Klumpers
Dept. Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Theo H
TH
Smit
School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, Massachusetts, 02138, United States of America; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, Massachusetts 02115, United States of America.
David J
DJ
Mooney
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D008954:Models, Biological; D012863:Skeleton / Q000196:embryology / Q000254:growth & development*; D013314:Stress, Mechanical