Analysis of the Relationship between Peak Stress and Proteoglycan Loss following Injurious Compression of Human Post-mortem Knee and Ankle Cartilage

Abstract

While traumatic joint injuries are known to increase the risk of osteoarthritis (OA), the mechanism is not known. Models for injurious compression of cartilage may identify predictors of injury that suggest a clinical mechanism. We investigated the relationship between peak stress during compression and glycosaminoglycan (GAG) loss after injury for knee and ankle cartilages. Human cartilage explant disks were harvested post-mortem from the knee and ankle of three organ donors with no history of OA and subjected to injurious compression to 65% strain in uniaxial unconfined compression at 2 mm/s (400%/s). The GAG content of the conditioned medium was measured 3 days after injury. After injury of knee cartilage disks, damage was visible in 18 of 39 disks (36%). Three days after injury, the increase in GAG loss to the medium (GAG loss from injured disks minus GAG loss from location-matched uncompressed controls) was 1.5+/-0.3 microg/disk (mean +/- SEM). With final strain and compression velocity held constant, we observed that increasing peak stress during injury was associated with less GAG loss after injury (P<0.001). In contrast, ankle cartilage appeared damaged after injury in only 1 of 16 disks (6%), there was no increase in GAG loss (0.0+/-0.3 microg/disk), and no relationship between peak stress and increase in GAG loss was detected (P=0.51). By itself, increasing peak stress did not appear to be an important cause of GAG loss from human cartilage in our injurious compression model. However, we observed further evidence for differences in the response of knee and ankle cartilages to injury.

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

“…Mechanical injury combined with TNF␣ treatment and IL-6/sIL-6R treatment resulted in the greatest increase in GAG loss. This combination had far less effect in ankle cartilage compared with knee cartilage (Figure 2), which is consistent with previous observations that ankle cartilage does not exhibit the same extent of mechanical damage as knee cartilage for the mechanical injury parameters used here (36), and that chondrocyte biosynthesis in ankle cartilage does not decrease as much as in knee cartilage when subjected to cytokines such as IL-1 (32).…”

“…Macroscopic tissue changes were similar in elliptical appearance to those described previously using our group's human cartilage injury model (36). After injury, samples were immediately placed in treatment medium.…”

Treatment of osteochondral defects of the talus

“…There appears to be a net anabolic response to injury in the ankle cartilage and a net catabolic response in the knee. 26,181,311 Ankle cartilage may be more resistant to osteoarthritis development for a number of reasons, including higher equilibrium and compressive moduli, better intercellular communications, increased resistance to inflammatory molecules, increased Fluorochrome labels were injected at 3 (oxytetracyclin; yellow arrow), 6 (calcein; green arrow), and 9 weeks (alizarin; red arrow) to analyze the mineral apposition rate. Calcein was best visible, followed by oxytetracyclin and alizarin, respectively.…”

“…Extrapolation to the ankle joint is unreliable because of the differences in cartilage properties, joint congruence, and response to injury. 26,181,234,311 One study specifically investigated PRP for talar OCDs. 280 Thirty patients received three weekly intra-articular injections of hyaluronic acid or PRP.…”

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

“…Although the consequences of GAG loss in terms of the biomechanical properties of articular cartilage have been examined in previous studies (23,24), the implications for chondrocyte survival and function are not known. To create a model of partial GAG loss, cartilage explants were treated with chondroitinase ABC.…”