Correlation between synthetic activity and glycosaminoglycan concentration in epiphyseal cartilage raises questions about the regulatory role of interstitial pH

Boustany, Nada N.; Gray, Martha L.; Black, Ann C.; Hunziker, Ernst B.

doi:10.1002/jor.1100130513

Cited by 23 publications

(9 citation statements)

References 11 publications

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“…The specific mechanisms by which chondrocytes detect mechanical signals and convert them to an intracellular biochemical response are not fully understood. However, depending on the mechanical condition applied (e.g., shear forces, tensile stress, compression, hydrostatic pressure), several signal transduction pathways have previously been found to be involved, including integrin-mediated pathways, stretchactivated or -inactivated ion channels, the cytoskeleton, decreased pH, electrical streaming potentials, nitric oxide, or activating second messenger systems (Boustany et al 1995;Das et al 1997;Millward-Sadler et al 2000;Wright et al 1996). Thus, the mechanical signal perceived by the chondrocytes influences the pathways subsequently used by the cells, resulting in different metabolic activities.…”

Section: Discussionmentioning

confidence: 99%

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading

2006

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Articular cartilage in vivo experiences the effects of both cell-regulatory proteins and mechanical forces. This study has addressed the hypothesis that the frequency of intermittently or continuously applied mechanical loads is a critical parameter in the regulation of chondrocyte collagen biosynthesis. Cyclic compressive pressure was applied intermittently to bovine articular cartilage explants by using a sinusoidal waveform of 0.1-1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5-20 s followed by a load-free period of 10-1,000 s. These loading protocols were repeated for a total duration of 6 days. In separate experiments, cyclic loading was continuously applied by using a sinusoidal waveform of 0.001-0.5 Hz frequency and a peak stress of 1.0 MPa for a period of 3 days. Unloaded cartilage discs of the same condyle were cultured in identically constructed loading chambers and served as controls. We report quantitative data showing that (1) no correlation exists between the relative rate of collagen synthesis expressed as the proportion of newly synthesized collagen among newly made proteins and either the frequency of intermittently or continuously applied loads or the overall time cartilage is actively loaded, and (2) individual protocols of intermittently applied loads can reduce the relative rate of collagen synthesis and increase the water content, whereas (3) continuously applied cyclic loads always suppress the relative rate of collagen synthesis compared with that of unloaded control specimens. The results provide further experimental evidence that collagen metabolism is difficult to manipulate by mechanical stimuli. This is physiologically important for the maintainance of the material properties of collagen in view of the heavy mechanical demands made upon it. Moreover, the unaltered or reduced collagen synthesis of cartilage explants might reflect more closely the metabolism of normal or early human osteoarthritic cartilage.

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Section: Discussionmentioning

confidence: 99%

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading

2006

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“…Acidification of the extracellular pH has been shown to modify protein and proteoglycan synthesis in intervertebral disc explants (9) and to inhibit matrix synthesis in human chondrocytes (10) and calf epiphyseal cartilage (5). A bimodal response to extracellular pH has been noted on matrix synthesis for bovine chondrocytes (11, 12), calf epiphyseal cartilage (13), and intervertebral disc slices (9), where matrix synthesis is greatest at normal cartilage pH (pH 7.0−7.2) (12) or at extracellular pH values close to that found for the disc in vitro (about pH 6.9−7.2) (9), and alkalinization or acidification will decrease matrix synthesis.…”

Section: Introductionmentioning

confidence: 99%

Effect of Extracellular pH on Matrix Synthesis by Chondrocytes in 3D Agarose Gel

Urban

Cui

et al. 2007

Biotechnology Progress

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In cartilage tissue engineering, the determination of the most appropriate cell/tissue culture conditions to maximize extracellular matrix synthesis is of major importance. The extracellular pH plays an important role in affecting energy metabolism and matrix synthesis by chondrocytes. In this study, chondrocytes were isolated from bovine articular cartilage, embedded in agarose gel, and cultured at varied pH levels (7.3-6.6). Rate of lactate production, total glycosaminoglycan (GAG) and collagen synthesis, as well as total cell numbers and cell viability were evaluated after culturing for up to 7 days. The results showed the rate of lactic acid production over the 7-day culture was significantly affected by extracellular pH; acidic pH markedly inhibited the production of lactate. Also, a biphasic response to extracellular pH in regard to total GAG synthesis was observed; the maximum synthesis was seen at pH 7.2. However, the collagen synthesis was not pH-dependent within the pH range explored. In addition, within the conditions studied, total cell numbers and cell viability were not significantly affected by extracellular pH. In conclusion, even minor changes in extracellular pH could markedly affect the metabolic activities and biosynthetic ability of chondrocytes. Consequently, the control of extracellular pH condition is crucially important for successful cartilage tissue engineering and for the study of chondrocyte physiology and functions.

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“…Each of these physical phenomena may potentially act as a "mechano-ligand" activating or inhibiting one or more signaling pathways. Prior studies have often focused on the effects of one or a few of these components of compressive loading such as negative fixed charge density (26) or interstitial pH (22,29,30). Recent studies have also demonstrated that mechanical stretching of chondrocytes can increase nitric oxide production (31) and alter membrane transport phenomena, resulting in proliferative changes (32).…”

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confidence: 99%

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

Fanning

Emkey

Smith

et al. 2003

Journal of Biological Chemistry

118

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Articular chondrocytes respond to mechanical forces by alterations in gene expression, proliferative status, and metabolic functions. Little is known concerning the cell signaling systems that receive, transduce, and convey mechanical information to the chondrocyte interior. Here, we show that ex vivo cartilage compression stimulates the phosphorylation of ERK1/2, p38 MAPK, and SAPK/ERK kinase-1 (SEK1) of the JNK pathway. Mechanical compression induced a phased phosphorylation of ERK consisting of a rapid induction of ERK1/2 phosphorylation at 10 min, a rapid decay, and a sustained level of ERK2 phosphorylation that persisted for at least 24 h. Mechanical compression also induced the phosphorylation of p38 MAPK in strictly a transient fashion, with maximal phosphorylation occurring at 10 min. Mechanical compression stimulated SEK1 phosphorylation, with a maximum at the relatively delayed time point of 1 h and with a higher amplitude than ERK1/2 and p38 MAPK phosphorylation. These data demonstrate that mechanical compression alone activates MAPK signaling in intact cartilage. In addition, these data demonstrate distinct temporal patterns of MAPK signaling in response to mechanical loading and to the anabolic insulin-like growth factor-I. Finally, the data indicate that compression coactivates distinct signaling pathways that may help define the nature of mechanotransduction in cartilage.

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Correlation between synthetic activity and glycosaminoglycan concentration in epiphyseal cartilage raises questions about the regulatory role of interstitial pH

Cited by 23 publications

References 11 publications

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading

Effect of Extracellular pH on Matrix Synthesis by Chondrocytes in 3D Agarose Gel

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

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