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

Abstract

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.

Acetylation reduces SOX 9 nuclear entry and ACAN gene transactivation in human chondrocytes

“…In line with the unaffected COL2A1 levels that we report herein, Wolf et al . reported that the rate of COL2A1 synthesis is unaffected by intermitted mechanical loading in cartilage explants (Wolf et al ., 2007). As mentioned, SOX9 expression was higher following loading at 0.05 MPa for 30 min than under unloaded conditions (fourfold; Fig.…”

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

“…These mechanical stimuli are important factors in the maintenance of normal structure and function of the articular cartilage. Periodic mechanical stress, as a special type of mechanical stimulation, can be used to advantage to simulate in vivo physiological mechanical conditions, enhancing the quality of tissue-engineered cartilage by promoting chondrocyte proliferation, migration, and matrix synthesis, which plays an important role in the repair of articular cartilage injury (2)(3)(4)(5). However, the mechanisms involved in chondrocytes to detect and respond to periodic mechanical stress have not been identified.…”

Proteomic Analysis Reveals a New Benefit of Periodic Mechanical Stress on Chondrocytes

“…In our quantitative protein analysis, we found that the protein level of type I collagen, which is always present in fibrocartilage, was significantly suppressed, while the protein level of type II collagen required in articular cartilage showed no significant change after periodic mechanical stress [31]. Not only was type I collagen reduced, but type III, type V, type VI and other related collagens which are closely connected to fibrosis were also decreased after periodic mechanical stress.…”