Viscosupplementation of synovial fluid with xanthan gum for treatment of osteoarthritis and its clearance kinetics in the rabbit knee joint.

BACKGROUND: Injection of xanthan gum (XG) has been demonstrated to reduce the symptoms and progression of osteoarthritis (OA) in experimental models. Due to its high viscosity and stability, it may restore the rheological homeostasis of osteoarthritic synovial fluid (SF), and avoid numerous intra-articular injections. OBJECTIVE: The present study investigated the effect of XG on the rheological properties of SF, and determined its residence time in the rabbit joint cavity. METHODS: Rabbit knees were subject to intra-articular injection with XG or XG labeled with green fluorescence, and the SF was collected at different time. Rheological properties of SF with XG injected were compared with those with sodium hyaluronate injected. Resistance to oxidant damage was tested by adding H2O2 to the viscosupplement. Fluorescence intensity was measured for the SF with XG labeled with green fluorescence. RESULTS: Results showed that XG could significantly improve the SF viscosity at 24, 96, 168 h, and increase the storage moduli (G') and loss moduli (G″) tested at frequency of 0.5 and 2.5 Hz. SF with XG injection exhibited a gel-like behavior at 24 h, in that G' exceed G″ over the entire oscillation frequency range. XG preparation had a high resistance to oxidant damage. Half-life of XG in the joint cavity was 35.9 h, with clearance obeying first-order kinetics. CONCLUSIONS: Intra-articular injection of XG could improve the rheological properties of SF, and this effect could last for several days.

Hyaluronic acid in combination with chondroitin sulfate and hyaluronic acid improved the degeneration of synovium and cartilage equally in rabbits with osteoarthritis.

The purpose of this study was to compare the chondroprotective effects of chondroitin sulfate (CS)-hyaluronic acid (HA) (CS-HA) injection and HA injection in an experimental model of osteoarthritis. After induction of osteoarthritis in rabbits, 28 rabbits were randomized into four groups: control group, 'HA' group, 'CS' group, and 'CS-HA' group. After 7 days, rabbits in the control group, 'HA' group, 'CS' group and 'CS-HA' group were respectively treated with normal saline, HA, CS, or CS-HA injection in the knees. All animals were treated once weekly. The animals were treated continuously for 5 weeks. Histological and biochemical evaluations were performed. As shown by histological observation, CS-HA injection treatment showed a chondroprotective effect on osteoarthritis. However, the histological scores of 'HA' group and 'CS-HA' group were not significantly different (p > 0.05). The results of biochemical evaluation showed that the expression levels of IL-1ß, TNF-α, TIMP-1 and NO in synovial fluid of treated groups were all different from the control group (p < 0.05). However, the expression levels of these biochemical molecules in three treated groups were not significantly different (p > 0.05). In conclusion, CS-HA injection showed no obvious advantage over HA injection in osteoarthritis treatment.

Use of induction promoters to regulate hyaluronan synthase and UDP-glucose-6-dehydrogenase of Streptococcus zooepidemicus expression in Lactococcus lactis: a case study of the regulation mechanism of hyaluronic acid polymer.

AIMS: To determine the effects of the ratios of hyaluronan synthase expression level to precursor sugar UDP-GlcA biosynthesis ability on the molecular weight (MW) of hyaluronic acid (HA) in recombinant Lactococcus lactis. METHODS AND RESULTS: The genes szHasA (hyaluronan synthase gene) and szHasB (UDP-glucose-6-dehydrogenase gene) of Streptococcus zooepidemicus were introduced into L. lactis under the control of nisA promoter and lacA promoter respectively, resulting in a dual-plasmid controlled expression system. The effects of the ratios of hyaluronan synthase expression level to the precursor sugar UDP-GlcA biosynthesis ability under different induction concentration collocations with nisin and lactose on the MW of HA in recombinant L. lactis were determined. The results showed that the final weight-average molecular weight () of HA correlated with the relative ratios of HasA (hyaluronan synthase) expression level to the concentration of UDP-GlcA. CONCLUSIONS: Regulating the relative ratios of HasA expression level to the precursor sugar biosynthesis ability was an efficient method to control the size of HA. SIGNIFICANCE AND IMPACT OF THE STUDY: This study put forward a guide to establish an efficacious way to control the size of HA in fermentation.

Effects of a hyaluronic acid and low molecular weight heparin injection on osteoarthritis in rabbits.

An osteoarthritis (OA) model was created in the knees of rabbits by injecting them with 0.3 mL of sterile papain solution in order to evaluate the effects of a hyaluronic acid (HA) and low molecular weight heparin (LMWH) injection on osteoarthritis. HA-LMWH, LMWH, and HA were injected into animals once weekly. After 5 weeks of treatment, the animals were sacrificed and the effects of the injections on osteoarthritis were evaluated by histological assessment. HA levels in cartilage and the levels of IL-1ß and TNF-α expression in synovial fluids were determined. As shown by histological observation, recovery of the synovium and cartilage of animals injected with HA-LMWH was better than that in animals injected with HA or LMWH. HA levels in cartilage of animals injected with HA-LMWH were much higher than those of the control group. The levels of IL-1ß expression in synovial fluids of animals injected with HA-LMWH were lower than those in other animals. The levels of TNF-α expression in synovial fluids of animals injected with HA-LMWH were much lower than those in the controls. In conclusion, HALMWH injection had a favorable anti-inflammatory and therapeutic effect on experimental OA.