Dishing up bone formation

ow cells connect to each other and to the extracellular matrix (ECM) was a sticky issue in the early 1980s. Integrins, molecules that hook the cy-toskeleton to ECM proteins such as collagen and fibronectin, hadn't been discovered, but evidence for a link between external and internal fibers was mounting. For example, Irwin Singer (1979) observed that extra-cellular fibronectin molecules closely approached—or possibly attached to— intracellular actin. Several researchers postulated that membrane-spanning receptors made the connection. A pair of papers by post-doc Wen-Tien Chen of the University of California, San Diego, and his adviser S. H Jonathan Singer bolstered the idea that cells deploy different membrane receptors to couple with different components of the matrix. A new technique devised in Singer's lab gave the researchers a clearer look at the junction between cell and surface. They reared cells on a gelatin mat, which they could roll up like a carpet, freeze, and cut into thin slices. Staining the gap with two types of antibodies pinpointed proteins clustering on both sides of the membrane. When the researchers zoomed in on a type of contact called a focal adhesion, they saw no signs of fibronectin outside the cell, although it's a key component of some cell surface junctions (Chen and Singer, 1980). Fibronectin's absence meant that cells needed a second kind of receptor to attach to the extracellular fibers found in focal adhesions, the researchers hypothesized. A follow-up study that included more kinds of contacts (Chen and Singer, 1982). They found that fibronectin amassed in two kinds of interactions, but not in two others. Moreover, at one type of fibronectin-rich junction, microfilaments inside the cell ran Dishing up bone formation iroaki Kodama knew little about dental and bone research when he became an assistant professor at Tohoku Dental University. What he did know was cell culture technology, and he recognized the field's need for a clonal cell line " which retains as far as possible a normal ability to differentiate into functional cells. " In 1979, he and his colleagues started establishing cell lines that differentiated into osteoblasts (bone-forming cells) rather than odontoblasts (dentin-forming cells). At that time, only a few primary bone cell cultures had been reported to show hints of in vitro bone formation (Binderman et al., 1979; Nijiweide et al., 1982). Kodama (RIKEN, Wako Saitama, Japan), says the secret to success was using the same cell culture method used to …