Time‐dependent changes in the response of cartilage to static compression suggest interstitial pH is not the only signaling mechanism

Abstract

The goal of the present study was to reexamine the role of interstitial pH in regulating the biosynthetic rate in cartilage tissue by addressing two research questions: (a) Do small, short-term changes in interstitial pH, induced independently by two different mechanisms (namely, by controlling the pH of the medium or by mechanical compression), result in biosynthetic rates commensurate with those expected from the "natural" relationship between interstitial pH and biosynthesis? and (b) Are the effects of changes in the pH of the medium or in compression the same for short-term (14-hour) and long-term (60-hour) exposures? Biosynthetic rates were estimated from incorporation of sulfate and proline into explants of bovine epiphyseal cartilage during the final 14 hours of culture. These rates decreased with decreasing pH of the medium, with increasing compression, and with decreasing native glycosaminoglycan content; or, expressed in terms of interstitial pH, acidification induced by compression or by lowering the pH of the medium resulted in a decreased biosynthetic rate, whereas interstitial acidification effected by increasing glycosaminoglycan content enhanced it. When the time for which tissue was exposed to changes in the pH of the medium was increased from 14 to 60 hours, the relationship between the biosynthetic rate and the pH remained constant whereas the relationship between the biosynthetic rate and compression was reversed. These data suggest that the transduction mechanisms underlying the response to pH of the medium and compression differ and that some adaptation or stimulation by modest levels of compression can occur with longer exposures. Interstitial pH is not the sole determinant of biosynthesis, and it cannot really account for the long-term response of cartilage tissue to static compression.

Long‐term intermittent shear deformation improves the quality of cartilaginous tissue formed in vitro

“…Tissues subjected to static compressive forces were also more hydrated, which probably reflected the smaller amount of collagen accumulated in these cultures [33, 361. These observations are in keeping with other studies that have demonstrated the detrimental effects of static compressive forces on the quality of the cartilage extracellular matrix [3,16,33,37].…”

Effects of confinement on the mechanical properties of self‐assembled articular cartilage constructs in the direction orthogonal to the confinement surface

“…Confinement either results in increased collagen organization as seen in the radial confinement experiment, or increased matrix synthesis as seen in the passive axial compression experiment. Although using immature bovine cartilage explants, Boustany et al 35 also found that static compression of <25% strain for 60 h increased the biosynthetic rate of GAG and collagen production, although the mechanical properties were not examined.…”

“…31 Following preconditioning, specimens were exposed to incremental stress relaxation, whereby they were exposed to 15 min constant strain increments until failure. A maximum of 11 increments were allowed (4,8,12,16,20,25,35,50,70, 100, and 130% strain). A strain rate of 6 mm/min was employed between constant-strain increments.…”

Mechanical Regulation of Mitogen-activated Protein Kinase Signaling in Articular Cartilage

“…The relatively simple case of a ramp-and-hold static compression of cartilage can result in transient interstitial fluid expression, cell deformation (25), increased osmolarity (26), decreased extracellular pH (27), changes in fixed charge density (28), and altered transport of soluble factors within the tissue (22). Each of these physical phenomena may potentially act as a "mechano-ligand" activating or inhibiting one or more signaling pathways.…”