Ectopic expression of tenascin-C.

We read, with much interest, the recent Research Article by Järvinen et al. (Järvinen et al., 2003), in which the authors show that, after removing the cast from an immobilized rat hind leg, within 8 weeks tenascin-C (TN-C) expression is increased in tendon and the myotendinous junction, but there is no de novo appearance of TN-C in skeletal muscle connective tissue. The authors extensively criticize our earlier paper (Flück et al., 2000), in which we concluded that loading of the chicken ALD muscle was sufficient to induce rapid ectopic TN-C expression in endomysial fibroblasts of skeletal muscle. Järvinen at al. argue that our results are merely caused by a response to muscle injury and the subsequent inflammatory reaction. We would like to respond to these statements because the experiment by Järvinen et al. is so vastly different from ours that the conclusion, 'Mechanical loading... does not induce de novo synthesis in the skeletal muscle', as stated in the title of their paper, is not justified. We investigated the tissue 4 hours after applying an acute load to a healthy muscle; Järvinen et al. looked only at a single time point 8 weeks after reloading an immobilized (atrophied) muscle. It is possible that an acute burst of TN-C expression occurs over 8 weeks after remobilization (Flück et al., 2003). Moreover, the image of the muscle tissue hybridized with the TN-C probe in the Järvinen et al. paper (Fig. 4) is taken at low magnification (5×), and thus mRNA signals in single endomysial fibroblasts are not visible. In our paper, we did not dismiss the possibility that the ectopic TN-C expression we observed was at least in part due to an inflammatory reaction. Nevertheless, Järvinen et al. clearly misquote us when they state in their Discussion, 'However, it is worth noting that Flück et al. (Flück et al., 2000) reported an almost 50% increase in the mass of the loaded muscle as soon as 4 hours after the beginning of elongation, concomitant with a marked early infiltration of inflammatory cells (macrophages and neutrophils) and widening of the endomysial spaces in the loaded muscle.' In fact, although we duly reported the evidence for early edema, we also demonstrated that TN-C expression after 4 hours of loading did not correlate with macrophage invasion, which we observed (by means of a specific antibody) only after 24 hours. Although there is no doubt that the supraphysiological …