Physiological tissues adapt their structure and composition to functional demands. Since a major function of connective tissues is mechanical support, physical forces are believed to play a significant role in connective tissue growth and development. This thesis focuses on the response of epiphyseal plate chondrocytes to mechanical loading. A basic system theory approach is used as a framework for examining the complex interactions which exist between the applied signal, tissue matrix, cells, and measurable response.

Under physiological loading conditions, many events occur simultaneously within the tissue. These include deformation, streaming currents and potentials;​ fluid flow, changes in hydrostatic pressure, and physicochemical changes associated with consolidation. Any one or more of these events may act as a modulating signal to the cell. Experimental configurations which decouple these events and which provide a spatially uniform signal were used to probe and characterize the cellular response.

Reserve zone epiphyseal plate cartilage was harvested from newborn calves immediately after slaughter and maintained in organ culture for 2 days. For the next 12 hours tissue was subjected to one of three exposure conditions:​ (1) sinusoidal currents up to 1 mA/cm² at frequencies ranging from 0.1 to 100 Hz, (2) static compressive loads up to 3 MPa, and (3) physicochemical alterations of [SO₄^2-] (0.8 mM to 1.6 mM), [K⁺] (5.4 mM to 10.4 mM) or pH (5.5 to 7.9). During the exposure period, tissue was bathed in media containing ³⁵S-sulfate and ³H-proline to assess glycosaminoglycan and protein synthesis. In a separate series of experiments the kinetics of the response to mechanical loading was examined for step loading and step unloading.

The applied currents, which were similar to those expected to occur under in vivo loading conditions, did not significantly alter the incorporation of proline and sulfate over the 12 hour period. Under static loading conditions there was a dose-dependent depression in proline and sulfate incorporation. This depression was strongly dependent on compression for compressions greater than 35%. Proline incorporation was found to decrease under load in less than 1/2 hour, while sulfate incorporation decreases in 2 to 6 hours. The response to unloading following a 12 hour preload was not simply the inverse of the response to loading;​ proline incorporation exceeded control levels for 4 hours, while sulfate incorporation remained depressed for over 4 hours.

Because of the high negative fixed charge density of cartilage, compression leads to increases in interstitial cation concentration (e.g. [K⁺], [H⁺]) and decreases in anion concentration (e.g. [S02-]) consistent with Donnan equilibrium. Increasing [S0O-] did not alter the incorporation of sulfate under free swelling or loading conditions. When the potassium concentration was increased under unloaded conditions to levels expected to occur at 60% consolidation there was no detectable effect on either sulfate or proline incorporation. In contrast, adjustment of bath pH with bicarbonate led to changes in incorporation consistent with those seen under equivalent loading conditions.

The insensitivity of chondrocytes in organ culture to electric fields (and/or associated fluid flow) suggests that such fields either have a minimal effect on the total biosynthetic behavior of chondrocytes, or result in a very slow response by the chondrocytes. The dose-dependent response to static loads suggests that longitudinal growth rate is modulated, in part, by the time-average load. This response may be accounted for by the decreased interstitial pH which occurs with consolidation. Compression induced changes in [K⁺] and [SO4-] do not appear to influence the response to compressive loads. The nonlinear response seen when comparing step increases in load to step decreases suggests that the response to dynamic loads may not simply reflect the response to the time-average load.