HA-treated Group Research Articles

Sodium hyaluronate therapy in osteoarthritis: Arguments for a potential beneficial structural effect

Objectives: Currently, available therapies for managing osteoarthritis (OA) provide symptomatic relief. Theoretical evidence suggests that exogenous hyaluronan (HA) administered as an intra-articular injection may slow disease progression. The purpose of this review is to discuss cellular and immunologic effects of HA that could affect OA progression and to present data from a clinical trial that evaluated HA structural effects. Methods: The medical and scientific literature regarding the cellular, immunologic, and structural effects of HA on the joint environment and function are reviewed. Results: Cellular effects of exogenous HA that affect the joint include increasing endogenous HA synthesis, stimulating proteoglycan synthesis, and inhibiting the release of chondrodegrading enzymes. The immunologic effects of HA are inhibition of mononuclear cell phagocytosis and leukocyte migration, chemotaxis, and phagocytosis. Also, HA is a free radical scavenger. In a pilot study using arthroscopy, cartilage deterioration was less in the HA-treated group compared with the control group. Conclusions: Considerable evidence supports the positive effects of HA on joint cellular and immunologic function. However, further clinical studies are needed to determine whether these effects are valuable in altering the progression of OA. Semin Arthritis Rheum 30:19-25. Copyright © 2000 by W.B. Saunders Company

The effect of hyaluronic acid on experimental temporomandibular joint osteoarthrosis in the sheep

Purpose The purpose of this study was to test the effect of repeated injections of hyaluronic acid (HA) on the sheep model of osteoarthrotic temporomandibular joint (TMJ) disease. Materials and Methods Bilateral Osteoarthrosis (OA) was induced in the TMJs of six sheep. HA was injected into one joint on 7, 10, 14, 17, and 21 days postoperatively. Normal saline was injected into the contralateral joint. Three sheep were killed at 1 month and 3 at 3 months. The joints were removed and examined macroscopically and histologically. A special scoring system was applied following the modified Mankin's score to evaluate the histologic changes. Results The control group showed severe osteoarthrotic changes in the condyle, deviation in form from normal morphology, and marked marrow fibrosis. The HA-treated group showed less deviation from normal condylar morphology. The histologic scores at 1 month were HA 12.6, control 24.2 ( P <.001), and at 3 months were HA 6.9, control 18.9 ( P < .001). There was a significant difference in osteoarthrotic changes between HA-treated and control TMJs, with the HA-treated TMJs having less severe changes. Conclusion Repeated intraarticular injections of HA into a sheep TMJ with experimentally induced OA minimizes the extent of osteoarthrotic change when compared with the control joint. Thus, HA may have a role in preventing the progression of TMJ OA.

The Effect of Chronic Haloperidol Treatment on Dendritic Spines in the Rat Striatum

Previous studies have shown that schizophrenics, in comparison to controls, have reduced cortical spine density and smaller striatal spines. The current study in the rat was conducted to determine whether such differences could result from chronic neuroleptic treatment and whether they are correlated with neuroleptic-induced oral dyskinesias. Rats administered 1.5 mg/kg/day of haloperidol (HA) (n=28) or water (n=10) were tested for vacuous chewing movements (VCMs). After 6 months, rats were divided into low and high VCM groups; all but seven high VCM rats were sacrificed. These rats (withdrawn group) were withdrawn from HA for 4 weeks. Random electron micrographs of the striatum were analyzed for spine changes. Spine size was not significantly affected by HA (0.193 vs 0.174 μm2, HA and control, respectively) nor correlated with oral dyskinesias (0.191 vs 0.196 μm2, low and high VCM groups, respectively). These results suggest that smaller spines in schizophrenic striatum may be correlated with the disease rather than caused by neuroleptic treatment. Spine density decreased in the HA-treated group (32.7±9.5) in comparison to controls (53.7±7.3,P<0.001) and remained low in the withdrawn group (35.0±4.2,P<0.01). Spine density also decreased in both the low (37.3±9.9,P<0.01) and the high (28.0±7.0,P<0.000) VCM groups in comparison to controls. However, there was no significant difference between high and low VCM groups, suggesting that decreased spine density is independent of oral dyskinesias. These results suggest that the decreased spine density observed in schizophrenic cortex may be a result of neuroleptic treatment.

Immunolocalization of stromelysin, tumor necrosis factor (TNF) α, and TNF receptors in atrophied canine articular cartilage treated with hyaluronic acid and transforming growth factor β

Abstract Objective To evaluate the ability of hyaluronic acid (HA), with and without transforming growth factor β (TGF-β), to stabilize the catabolic processes associated with atrophy of articular cartilage. Animals 20 adult, skeletally normal, hound-type dogs. Procedure Dogs (20 to 30 kg) were randomly assigned to 1 of 5 groups. One group served as untreated controls. Bivalve casts were placed on the left hind limbs of the remaining 16 dogs to limit weightbearing and motion of the limb for 92 days. One group served as the cast control. Beginning on day 56, 3 groups received aseptic intra-articular injections in the left stifles of either 5 mg of HA or 5 mg of HA containing either 20 or 50 μg of TGF-β. Intra-articular injections were repeated at 4-day intervals until the end of the study. On day 92, stifles were harvested at necropsy. Medial femoral condyles were histologically processed, and the articular cartilage was stained for the presence of proteoglycans, stromelysin, tumor necrosis factor (TNF) α, and TNF receptors (p55 and p75). Results Decreased metachromasia was evident in the cartilage matrix of all cast groups, with the smallest decrease in the HA-treated group. Stromelysin was immunolocalized in articular cartilage of the cast (left) limbs of cast control and both HA/TGF-β-treated groups. TNF-α was localized in articular cartilage of all cast (left) and right limbs, except those of the HA-treated group. Receptors for TNF were observed in both limbs of untreated control and cast control groups and cast limbs of HA/TGF-β-treated groups. The receptors were not localized in the right limbs of the HA with or without TGF-β-treated groups. TGF-β did not decrease stromelysin or TNF-α or receptors at the doses used. Conclusions HA may mediate a chondrostabilizing influence on articular cartilage by down-regulating TNF-α. Importantly, HA appeared to exert its inhibitory influence on TNF-α, as well as stromelysin and TNF receptors, on a systemic basis. Clinical Relevance Results provide insight into the mode of action of HA as a therapeutic agent for arthritis and its stabilizing influence on cartilage metabolism. (Am J Vet Res 1996;57:1488-1496)

Effects of Hyaluronic Acid on Fibroblast Behavior in Peritoneal Injury

The process of intraperitoneal adhesion formation is affected by macrophages and fibroblasts which are major components of postsurgical peritoneal repair. Hyaluronic acid (HA) has been shown to affect cellular behavior. We studied the effects of HA on experimental adhesionsin vivoand itsin vitroeffect on cultured postsurgical macrophages and fibroblasts. Experimental adhesions were facilitated by laparotomy and localized peritoneal controlled trauma in two groups of rats (A, B). Postoperatively, group A received intraperitoneal (ip) treatment by HA (1 mg/kg) for 7 days, and group B, ip saline. The rats were then reoperated upon, and adhesions scored.In vitrostudies were performed on postsurgical macrophages and fibroblasts. Fibroblasts were obtained using a single-cell suspension technique by debridement of adhesions. The fibroblasts were cultured for 7 days, and their metabolic activity was assessed by the uptake of [3H]thymidine. Postoperative macrophages were obtained from the peritoneal fluid of the rats operated on, and their effect upon fibroblast [3H]thymidine uptake was studied in mixed cultures. The adhesion score of the HA-treated rats was smaller than the score of the saline-treated group. This observation suggests that ip treatment by HA may decrease adhesion formation in this rat model. [3H]Thymidine uptake by cultured postsurgical fibroblasts was significantly lower in the HA-treated group compared to that of controls.In vitroaddition of HA to cultured “saline fibroblast” resulted in a significant decrease in [3H]thymidine uptake, suggesting a direct effect of HA on postsurgical fibroblast metabolism. However, [3H]thymidine uptake by fibroblasts in mixed cultures with macrophages obtained from HA-treated rats was significantly increased. These observations suggest that HA may affect the process of peritoneal healing by direct effect on fibroblast metabolic activity, and indirectly via modification of the macrophage–fibroblast interrelationship.

The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep I. Gait analysis and radiological and morphological studies

Using a model of early osteoarthritis (OA) induced in ovine joints by medial meniscectomy, the intraarticular effects of two hyaluronic acid (HA) preparations (AHA and DHA) were investigated. DHA was an HA preparation with an average molecular weight (MW) of approximately 2.0 x 10(6) d, and AHA had a MW of approximately 8 x 10(5) d. Animals (n = 5) were injected intraarticularly with 1 mL (10 mg/mL) of either HA preparation once a week for 5 weeks beginning 16 weeks after initiation of arthropathy. Meniscectomized, saline (1.0 mL)-injected animals (n = 5) and nonoperated sheep (n = 5) were used for controls. Force-plate analysis of gait and radiographic changes in joints were evaluated in these groups before and after intraarticular treatment. At necropsy, cartilage gross morphology, osteophyte development, and cartilage histopathology were examined. Meniscectomized joints were characterized by erosions and fissuring of cartilage of the medial compartment with areas of decreased matrix staining for proteoglycans. Osteophytes were present at the medial joint margins. Saline-treated meniscectomized animals showed reduced loading of the operated limb using the force plate. Force-plate analysis of walking animals before and after treatment with either AHA or DHA indicated some normalization of joint loading. However, osteophyte scores for meniscectomized joints injected with AHA and DHA were higher after treatment than those of the corresponding saline-treated group. Although the gross cartilage damage was lower than in saline-treated controls for both the HA-treated groups, the histological scores did not support this conclusion. Indeed, the tibial score for the DHA group was higher than for the AHA group (P < .05). These studies confirmed previous reports that meniscectomy of sheep stifle (knee) joints resulted in matrix changes similar to those described for early OA in humans. Both HA preparations appeared to improve gait, suggesting decreased lameness. Increased joint loading associated with gait improvement may account for the higher osteophyte scores in the treated groups. However, cartilage damage with DHA was found to be higher than when the lower-MW HA preparation (AHA) was used.

Quantifying two-dimensional joint incongruity in the osteoarthrotic hip

Purpose The purpose of this study was to test the effect of repeated injections of hyaluronic acid (HA) on the sheep model of osteoarthrotic temporomandibular joint (TMJ) disease.Materials and Methods Bilateral Osteoarthrosis (OA) was induced in the TMJs of six sheep. HA was injected into one joint on 7, 10, 14, 17, and 21 days postoperatively. Normal saline was injected into the contralateral joint. Three sheep were killed at 1 month and 3 at 3 months. The joints were removed and examined macroscopically and histologically. A special scoring system was applied following the modified Mankin's score to evaluate the histologic changes.Results The control group showed severe osteoarthrotic changes in the condyle, deviation in form from normal morphology, and marked marrow fibrosis. The HA-treated group showed less deviation from normal condylar morphology. The histologic scores at 1 month were HA 12.6, control 24.2 (P <.001), and at 3 months were HA 6.9, control 18.9 (P < .001). There was a significant difference in osteoarthrotic changes between HA-treated and control TMJs, with the HA-treated TMJs having less severe changes.Conclusion Repeated intraarticular injections of HA into a sheep TMJ with experimentally induced OA minimizes the extent of osteoarthrotic change when compared with the control joint. Thus, HA may have a role in preventing the progression of TMJ OA.

Optimization as applied to large-scale 3-D human postural systems: A synthesis of concepts and approaches

Purpose The purpose of this study was to test the effect of repeated injections of hyaluronic acid (HA) on the sheep model of osteoarthrotic temporomandibular joint (TMJ) disease.Materials and Methods Bilateral Osteoarthrosis (OA) was induced in the TMJs of six sheep. HA was injected into one joint on 7, 10, 14, 17, and 21 days postoperatively. Normal saline was injected into the contralateral joint. Three sheep were killed at 1 month and 3 at 3 months. The joints were removed and examined macroscopically and histologically. A special scoring system was applied following the modified Mankin's score to evaluate the histologic changes.Results The control group showed severe osteoarthrotic changes in the condyle, deviation in form from normal morphology, and marked marrow fibrosis. The HA-treated group showed less deviation from normal condylar morphology. The histologic scores at 1 month were HA 12.6, control 24.2 (P <.001), and at 3 months were HA 6.9, control 18.9 (P < .001). There was a significant difference in osteoarthrotic changes between HA-treated and control TMJs, with the HA-treated TMJs having less severe changes.Conclusion Repeated intraarticular injections of HA into a sheep TMJ with experimentally induced OA minimizes the extent of osteoarthrotic change when compared with the control joint. Thus, HA may have a role in preventing the progression of TMJ OA.