Fursultiamine, a vitamin B1 derivative, enhances chondroprotective effects of glucosamine hydrochloride and chondroitin sulfate in rabbit experimental osteoarthritis.
OBJECTIVE
The therapeutic effect of glucosamine hydrochloride (GH) and chondroitin sulfate (CS) in combination with fursultiamine, a vitamin B1 derivative, on the development of cartilage lesions was investigated in an animal model of osteoarthritis (OA).


METHODS
The OA model was created by partial medial meniscectomy of the right knee joint (day 0). The rabbits were placed into three experimental groups: operated (OA) rabbits that received placebo treatment, OA rabbits that received GH (1000 mg/kg) + CS (800 mg/kg), and OA rabbits that received GH + CS + fursultiamine (100 mg/kg). Each treatment was initiated on day 3 and continued for 8 weeks. Macroscopic and histologic analyses were performed on the cartilage. The level of MMP-1 in OA cartilage chondrocytes was evaluated by immunohistochemistry.


RESULTS
Only the group receiving combined treatment with GH + CS + fursultiamine showed a significant reduction in the severity of macroscopic and histologic lesions on tibial plateau, which is the weight bearing cartilage surface of the tibia, compared with placebo-treated OA rabbits. This treatment group also revealed a small, but significant, decrease in the body weight gain of the rabbits. In cartilage from placebo-treated OA rabbits, a significantly higher percentage of chondrocytes in superficial layer stained positive for MMP-1 compared with unoperated control. Rabbits treated with the GH + CS + fursultiamine revealed a significant reduction in the level of MMP-1.


CONCLUSIONS
These results suggest that the chondroprotective effect of GH + CS is enhanced by the addition of fursultiamine in experimental OA. This effect was associated with a reduction in the level of MMP-1, which are known to play an important role in the pathophysiology of OA lesions.
Pharmacology Research Laboratories I, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka, 532-8686, Japan.
T
T
Kobayashi
K
K
Notoya
A
A
Nakamura
K
K
Akimoto
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D002809:Chondroitin Sulfates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D005666:Fursultiamin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005944:Glucosamine / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D013977:Tibia / Q000378:metabolism / Q000473:pathology
D020011:Protective Agents; D005666:Fursultiamin; D002809:Chondroitin Sulfates; D020781:Matrix Metalloproteinase 1; D005944:Glucosamine