title: The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. I. Gait analysis and radiological and morphological studies.
abstract: 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.
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories (University of Sydney), Royal North Shore Hospital of Sydney, St Leonards, NSW, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Ghosh
authors.forename: R
authors.initials: R
authors.lastname: Read
authors.forename: S
authors.initials: S
authors.lastname: Armstrong
authors.forename: D
authors.initials: D
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Marshall
authors.forename: P
authors.initials: P
authors.lastname: McNair
mesh_terms: D000818:Animals; D002356:Cartilage / Q000473:pathology; D004195:Disease Models, Animal; D005684:Gait / Q000187:drug effects / Q000502:physiology*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011859:Radiography; D012756:Sheep
chemical_list: D006820:Hyaluronic Acid