Chondrocytes in articular cartilage utilize mechanical signals from their environment to regulate their metabolic activity. However, the sequence of events involved in the transduction of mechanical signals to a biochemical signal is not fully understood. It has been proposed that an increase in the concentration of intracellular calcium ion ([Ca2+]i) is one of the earliest events in the process of cellular mechanical signal transduction. With use of fluorescent confocal microscopy, [Ca2+]i was monitored in isolated articular chondrocytes subjected to controlled deformation with the edge of a glass micropipette. Mechanical stimulation resulted in an immediate and transient increase in [Ca2+]i. The initiation of Ca2+ waves was abolished by removing Ca2+ from the extracellular media and was significantly inhibited by the presence of gadolinium ion (10 microM) or amiloride (1 mM), which have previously been reported to block mechanosensitive ion channels. Inhibitors of intracellular Ca2+ release (dantrolene and 8-diethylaminooctyl 3,4,5-trimethoxybenzoate hydrochloride) or cytoskeletal disrupting agents (cytochalasin D and colchicine) had no significant effect on the characteristics of the Ca2+ waves. These findings suggest that a possible mechanism of Ca2+ mobilization in this case is a self-reinforcing influx of Ca2+ from the extracellular media, initiated by a Ca2+-permeable mechanosensitive ion channel. Our results indicate that a transient increase in intracellular Ca2+ concentration may be one of the earliest events involved in the response of chondrocytes to mechanical stress and support the hypothesis that deformation-induced Ca2+ waves are initiated through mechanosensitive ion channels.

Summary:Chondrocytes in articular cartilage utilize mechanical signals from their environment to regulate their metabolic activity. However, the sequence of events involved in thc transduction of mechanical signals to a biochemical signal is not fully undcrstood. It has been proposed that an increase in the concentration of intracellular calcium ion ([Ca2+Ii) is one of the earliest events in the process of cellular mechanical signal transduction. With use of fluorescent confocal microscopy, [Ca2+], was monitored in isolated articular chondrocytes subjectcd to controlled deformation with the edge of a glass micropipette. Mechanical stimulation resulted in an immediate and transienl increasc in [&*+Ii. The initiation of Ca2+ waves was abolished by removing Ca2+ from the extraccllular mcdia and was significantly inhibited by the presence of gadolinium ion (10 pM) or amiloride (I mM), which have previously been reported lo block mechanosensitive ion channels.Inhibitors of intracellular Ca2+ release (dantrolene and 8-dielhylaminooctyl 3,4,5-trimethoxybenzoate hydrochloride) or cytoskeletal disrupting agents (cytochalasin D and colchicine) had no significant effect on the characteristics of the Ca2+ waves. These findings suggest that a possible mechanism of Ca2+ mobilization in this case is a self-reinforcing influx of Ca2+ from the extracellular media, initiated by a Caz+-permeable mechanosensitive ion channel. Our results indicate that a transient increase in intracellular Ca2+ concentration may be one of the earliest events involved in the response of chondrocytes to mechanical stress and support the hypothesis that deformation-induced Ca2+ waves are initiated through mechanosensitive ion channels.Articular cartilage is maintained in a balanced state of turnover by the chondrocyte cell population. These cells are highly sensitive to their biophysical environment and rely on mechanical signals together with genetic and other environmental factors to regulate their metabolic activity (29). Under physiological loading conditions, chondrocytes undergo significant changcs in shape due to deformation of the cartilage extracellular matrix (27,28,63), suggesting that cell deformation may serve as a signal in the process of mechanical signal transduction. The biological mechanisms by which such cellular deformation is transduced to an intracellular signal are still unclear but seem to involve the traditional intracellular second messenger pathways, such as production of cyclic adenosine

Twenty-five patients who had an acute Achilles tendon rupture were managed with an augmented repair using the gastrocnemius-soleus fascia. All patients healed their repair and there were no re-ruptures. There was one infection. Augmented repair allowed early functional recovery as evidenced by full ankle motion by four to eight weeks, full unassisted weight bearing by three weeks, cessation of braces by four weeks, and return to work by one to six weeks post-operatively. Augmentation adds a sufficient amount of collagen to allow early range of motion and weight bearing without re-rupture. Disadvantages included a long incision, soft tissue prominence, one infection, and sural nerve injury.

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