Effect of intermittent cyclic preloads on the response of articular cartilage explants to an excessive level of unconfined compression

Abstract

Mechanical loading of articular cartilage can influence chondrocyte metabolism and lead to alterations in cartilage matrix composition. Most previous studies have focused on the effect of cyclic loading on cartilage mechanical properties and proteoglycan synthesis. However, the role of proteoglycans synthesized from cyclically loaded cartilage in response to an acute overload has not been elucidated. Therefore, we conducted studies where low intensity, intermittent cyclic loading was applied to chondral explants prior to an acute unconfined compression on the tissue. The chondral explants were randomly assigned to three groups: 7, 14, and 21 days of 10 cycles of 0.2 Hz sinusoidal loading at 0.5 MPa followed by an unloaded interval of 3,600 s. All explants were then taken to 25 MPa of unconfined compression. Biochemical assays were conducted to determine the tissue proteoglycan and hydroxyproline contents. The results showed cyclic preloading increased the proteoglycan content and mechanically stiffened the explants, making them more resistant to matrix damage and cell death under 25 MPa of unconfined compression up to 14 days. After 21 days of cyclic loading, however, the explants lost compressive stiffness and suffered more extensive damage in the unconfined compression test. This study investigated the role of cyclic loading in response of chondral explants to a potentially damaging, acute overload. In the long term, these types of studies may help understand the role of preconditioning of articular cartilage for in vitro or even in vivo studies of blunt force trauma to a joint. ß

High levels of glucosamine–chondroitin sulfate can alter the cyclic preload and acute overload responses of chondral explants

“…However, data from our laboratory indicated that 21 days of cyclic loading does not significantly alter the percentage of live cells ($92%) in the explants compared to unstressed controls. 8 Additionally, cyclic compression did not statistically alter the specimen thickness, suggesting no change in tissue volume over time. 8 As proposed earlier by Torzilli et al, 19 cartilage cell membrane damage may directly relate to the amount of matrix compression.…”

“…8 Additionally, cyclic compression did not statistically alter the specimen thickness, suggesting no change in tissue volume over time. 8 As proposed earlier by Torzilli et al, 19 cartilage cell membrane damage may directly relate to the amount of matrix compression. In our current study the percentage of cell damage per unit compressive strain was significantly decreased in the cyclic preloaded explants cultured in the supplement (Fig.…”

“…The hypothesis of a previous study 8 was that the degenerative effect in mechanical properties was likely due to the production of MMPs (possibly MMP-3) as a result of intermittent cyclic compression at 0.5 MPa. 9 The hypothesis of our current study was that media supplementation would limit or mitigate the effect.…”

“…7 Recent studies in our laboratory show that low intensity, intermittent cyclic preloading of chondral explants prior to an acute overload yields an increase in the synthesis of tissue PGs, resulting in a less severe traumatic insult for an acute overload. 8 Between 14 and 21 days of cyclic preloading, the explants experience a significant PG loss that leads to a dramatic loss in mechanical properties. Acute overloading of the explanted tissue then yields matrix damage and cell death significantly greater than nonpreloaded controls.…”

Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear

“…8,9 For chronic stress, few in vitro models exist, usually through high loading cycles of dynamic compression. [10][11][12] Modeling shear damage to the surface, which could be classified as a form of chronic stress, has not been well evaluated in cartilage explant studies. This is despite the clinical association between shear damage and the development of osteoarthritis (OA).…”