Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis

Abstract

Objective: To examine the therapeutic efficacy of N-acetylglucosamine (GlcNAc) in rabbits with experimental osteoarthritis (OA).

Methods: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). In the first study, rabbits (six in each group) received intramuscular injections of GlcNAc or normal saline three times a week starting 1 week postoperatively. In the second study, rabbits (eight in each group) were injected intra-articularly with GlcNAc (either once or twice a week) or normal saline. In the third study, rabbits (seven in each group) were injected intra-articularly twice a week with either GlcNAc, hyaluronan, or normal saline. Animals were killed 8 weeks after ACLT for macroscopic and histological assessment of the knee joints.

Results: Intramuscular administration of GlcNAc in rabbits with experimental knee OA did not show chondroprotective effects but showed mild anti-inflammatory activity. In contrast, intra-articular administration of GlcNAc twice a week reduced cartilage degradation. Additionally, intra-articular GlcNAc also suppressed synovitis. Once a week intra-articular injections of GlcNAc did not demonstrate therapeutic efficacy. The chondroprotective efficacy of GlcNAc was better than that of viscosupplementation treatment with hyaluronan.

Conclusion: Intra-articular GlcNAc has chondroprotective and anti-inflammatory activity in experimental OA.

Figure 1

Morphological grading of femoral condyles (A) and tibial plateaus (B) in rabbits with unilateral ACLT treated with intra-articular GlcNAc or saline. A total of 24 rabbits underwent unilateral ACLT. Eight rabbits were injected intra-articularly with GlcNAc once a week in a volume of 0.3 ml per knee joint. The single dose of GlcNAc for each injection was 80 mg. The second group of rabbits received intra-articular injections of GlcNAc twice a week in a volume of 0.3 ml per knee joint (80 mg for each injection). A control group of seven animals was injected intra-articularly twice a week with normal saline (0.3 ml per joint). All intra-articular injections started 1 week postoperatively and were performed for a period of 7 weeks.

Figure 2

Gross morphological grading of femoral condyles (A) and tibial plateaus (B) in rabbits with unilateral ACLT treated with intra-articular GlcNAc, hyaluronan, or saline. A total of 21 rabbits underwent unilateral ACLT. Seven rabbits were injected twice a week intra-articularly with GlcNAc in a volume of 0.3 ml per knee joint. The single dose of GlcNAc for each injection was 80 mg. The second group of rabbits received twice a week intra-articular injections of hyaluronan (3 mg/0.3 ml per joint). The control group of seven animals was injected twice a week intra-articularly with normal saline (0.3 ml per joint). All intra-articular injections started 1 week postoperatively and were performed twice a week for a period of 7 weeks.

Figure 3

Digital image analysis of the lesion size in femoral condyles (A) and tibial plateaus (B). Digital image analysis of the lesion size was performed in seven animals with unilateral ACLT treated with intra-articular GlcNAc and in seven animals with unilateral ACLT treated with intra-articular saline.