Biosynthetic response and mechanical properties of articular cartilage after injurious compression

Abstract

Traumatic joint injury is known to produce osteoarthritic degeneration of articular cartilage. To study the effects of injurious compression on the degradation and repair of cartilage in vitro, we developed a model that allows strain and strain rate-controlled loading of cartilage cxplants. The influence of strain rate on both cartilage matrix biosynthesis and mechanical properties was assessed after single injurious compressions. Loading with a strain rate of 0.01 SKI to a final strain of 50'% resulted in no measured effect on the cells or on the extracellular matrix, although peak stresses reached levels of about 12 MPa. However, compression with strain rates of 0.1 and 1 s-' caused peak stresses of approximately 18 and 24 MPa, respectively, and resulted in significant decreases in both proteoglycan and total protein biosynthesis. The mechanical properties of the explants (compressive and shear stiffiiess) were also reduced with increasing strain rate. Additionally, cell viability decreased with increasing strain rate, and the remaining viable cells lost their ability to exhibit an increase in biosynthesis in response to low-amplitude dynamic mechanical stimulation. This latter decrease in reparative response was most dramatic in the tissue compressed at the highest strain rates. We conclude that strain rate (like peak stress or strain) is an important parameter in defining mechanical injury, and that cartilage injuriously compressed at high strain rates can lose its characteristic anabolic response to low-amplitude cyclic mechanical loading.

Mechanical injury of cartilage explants causes specific time‐dependent changes in chondrocyte gene expression

“…Another limitation is the use of newborn tissue. We and other investigators have previously studied the effects of injury on cell viability and ECM degradation in the presence and absence of exogenous cytokines, using both immature and adult cartilage from bovine and human joint surfaces, with the finding that certain responses vary with age (12,13,44). It will be important to extend the present study to identify any age-or disease-dependence of changes in gene expression caused by mechanical injury.…”

“…A single injurious compression of cartilage has been shown previously to decrease ECM biosynthesis rates, compromise mechanical properties, and reduce chondrocyte viability (12)(13)(14)(15)(16)22). We undertook this study to determine if changes also occur at the level of gene expression, and to determine whether the changes are general or are specific to certain genes.…”

“…After equilibration of the explants, a custom-designed incubator-housed loading apparatus (25) was used ( Figure 1A) to injuriously compress 36 cartilage disks from each joint, while the remaining 12 disks served as free swelling controls. Cartilage samples to be injured were placed individually into a polysulfone chamber ( Figure 1B), which allows radially unconfined compression of the disk by impermeable platens (12,13,15). The measured thickness of the cartilage disk just prior to loading was recorded, and the zero-strain position was identified by the point of first contact between the loading platen and the cartilage surface.…”

“…Color figure can be viewed in the online issue, which is available at http://www.arthritisrheum.org. loss to the medium in similar bovine cartilage explants (12,13,15,22,23).…”

“…Mechanical loads applied in vitro range from single compressions of up to 50% strain (12)(13)(14)(15)(16)(17) to large-amplitude cyclic compression at varying frequencies (ϳ0.05-0.3 Hz) for up to 2 hours (18)(19)(20)(21). Injurious mechanical compression of cartilage in vitro can damage the extracellular matrix (ECM), leading to increased water content (12,16,18,22), decreased stiffness (12,22), increased hydraulic permeability (20), loss of glycosaminoglycan (GAG) to the culture medium (12)(13)(14)(15)17,20,22,23), loss of collagen to the medium (20), and temporary denaturation of collagen in the tissue (16,18,20,21). In addition, injurious mechanical compression can lead to cell death by both apoptosis and necrosis (14,16,19,(21)(22)(23), as well as decreased matrix biosynthesis rates in the remaining viable cells after injury (12).…”