Decrease in the basal levels of cytosolic free calcium in chondrocytes during aging in culture: possible role as differentiation-signal.
Cell- and matrix-related parameters, which characterize the aging and differentiation process of cartilage in vivo, were measured in cultured chick epiphyseal chondrocytes during maintenance in a suspension culture for 34 days. A gradual decrease in the rates of proliferation and an increase in the size of the cells were observed. Ultrastructural examination revealed increased vacuolization and appearance of glycogen-storing pools. The rate of proteoglycan synthesis gradually increased. Age-related changes in the composition of the proteoglycan consisted of an increase in the ratio of keratan sulfate/chondroitin sulfate. The results indicate that the process of aging in culture resembles maturation and differentiation of cartilage tissue in vivo. The levels of cytosolic free calcium ions ([Ca2+]i) were measured in fura-2-loaded cells during the course of aging in culture. A gradual decrease in [Ca2+]i was observed. In 5-day cultures, a value of 184 nM [Ca2+]i was measured; this value decreased to 61 nM in 34-day cultures. On the basis of the present data and the previous results, which showed that cartilage-derived growth factors caused a decrease in [Ca2+]i, concomitantly with enhancing differentiation, whereas factors which elevated [Ca2+]i caused an increase in proliferation and a decrease in proteoglycan synthesis, we suggest a model for control of chondrocyte differentiation and aging. The model suggests that the rate of differentiation may be paced by changes in steady-state levels of [Ca2+]i.
Beit-Or
A
A
Department of Chemical Pathology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Nevo
Z
Z
Kalina
M
M
Eilam
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation; D002642:Chick Embryo; D003600:Cytosol / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000302:isolation & purification; D007700:Kinetics; D008854:Microscopy, Electron; D015398:Signal Transduction; D013997:Time Factors
D006025:Glycosaminoglycans; D002118:Calcium