title: Pharmacological effects of novel cross-linked hyaluronate, Gel-200, in experimental animal models of osteoarthritis and human cell lines.
abstract: OBJECTIVE
  To study the pharmacological effects of Gel-200, cross-linked hyaluronate.
  
  
  METHODS
  We examined the chondroprotective, anti-inflammatory and analgesic effects of Gel-200 in experimental animal models for osteoarthritis (OA) and in a human synovial sarcoma cell line and normal human articular chondrocytes.
  
  
  RESULTS
  In the OA model, a single-dose intra-articular (IA) injection of Gel-200 significantly suppressed cartilage degeneration and reduced synovitis of the knee joint. In the joint pain model, Gel-200 significantly suppressed pain responses for 4 weeks after injection. The residual property of Gel-200 in the knee joint tissue was investigated in rabbits. The mean residual ratio of injected Gel-200 in the synovium was 3.3% (95% confidence interval [CI], 2.4-4.2) at 28 days after the injection. The long-lasting analgesic effect of Gel-200 might be explained by its high residual ratio in the joint. In addition, we investigated the mechanism of action of Gel-200 in a human synovial sarcoma cell line and normal human articular chondrocytes. Gel-200 inhibited IL-1β-induced production of MMP-1, 3 and 13 in human chondrocytes and production of prostaglandin E2 in human synoviocytes in a concentration-dependent manner, respectively.
  
  
  CONCLUSIONS
  A single-dose IA injection of Gel-200 exerts chondroprotective and anti-inflammatory effects in the experimental OA model, and long-lasting analgesia in the joint pain model, suggesting the beneficial multimodal function of Gel-200 against symptomatic OA patients.
authors.affiliation: Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan. Electronic address: keiji.yoshioka@seikagaku.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kisukeda
authors.affiliation: Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Nodera
authors.affiliation: Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D001707:Biopsy, Needle; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D016001:Confidence Intervals; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005782:Gels / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D008297:Male; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D005782:Gels; D006820:Hyaluronic Acid; D015232:Dinoprostone
keywords: Cross-linked HA; Gel-200; Osteoarthritis; Photo-gelation technology