Abstract
Background
Osteoarthritis (OA), is characterised with a loss of cartilage and pain in affected joints. It is this pain which most patients associate with their condition. Intra-articular (IA) hyaluronan (HA) has been shown to reduce the pain associated with OA both in animal models and in clinical trials. There are purified HA available and in recent years hyaluronan hydrogels, where the material has been cross-linked into networks, have become available. One of these cross-linked HA hydrogels is Durolane¯. This study has sought to evaluate the effect of Durolane in an in vivo model of osteoarthritis.
Methods
Mice (C57BL/6, 12 weeks) were obtained from Jackson Labs and all protocols were approved by Rush IACUC. Joint injury was initiated by TGFb1 injection as described [1]. Mice were given IA injections of 200 ng TGFb1, at days 1 and 3 delivered in a 6 ul volume into the rear right knee joint only. Twenty four hours after the second injection of TGFb1 10 ul of Durolane was injected into the same knee joint. All animals were exercised daily on a treadmill to induce tissue degeneration. Three groups of animals were evaluated: Naïve (n = 4), TGFb1 + saline (n = 5) and TGFb1 + Durolane (n = 5). Running performance was monitored daily and 15 days post injections, gait was assessed quantitatively using the TreadScan gait analysis system (CleverSys).
Results
Combined treatment of IA TGFb1 and treadmill running results in rapid and reproducible OA-like joint tissue remodelling in injected knee joints, including cartilage erosion, synovial and joint capsule fibrosis and chondrophyte accumulation along joint margins [2]. It was clear that the injections of TGFb1 + saline into the rear right knee joint caused impairment in gait, such as limping and difficulty to maintain treadmill running. In comparison the TGFb1 + Durolane treated animals showed running behaviours similar to that seen in untreated naïve mice. Quantitative assessment of gait using the TreadScan system, for a number of gait parameters, confirmed that Durolane returned the gait in these animals with induced OA closer to the gait of naïve animals. For example the stance time, described as time elapsed while the foot is in contact with the tread in its stance phase, being 185.81 ms (SD 34.85) for naïve, 249.67 ms (SD 37.58) for TGFb1 + saline and 214.86 ms (SD 28.1) for TGFb1 + Durolane treated animals. Single factor ANOVA for primary comparison between TGFb1 + Durolane and TGFb1 + saline provided a significant improvement for the Durolane group (p < 0.05).
Conclusions
This study has demonstrated that a single IA injection of Durolane can improve gait in this non-surgical model of OA confirming earlier data that Durolane provides anti-nociceptive effects in a model of joint pain [3].
