Table 2.
Effects of hyaluronan (hyaluronic acid) and hylans on the extracellular matrix
| Effect | Reference | Experimental model; treatment | MW-dependent | Dose-dependent |
| Enhanced HA synthesis | Smith & Ghosh, 1987 [21] | Synovial fibroblasts of patients with normal joints and with OA; HA of various MWs and concentrations | Yes | Yes |
| Increased synthesis of chondroitin sulfate | Kawasaki et al., 1999 [52] | Rabbit chondrocytes; various HA doses | N/A | Yes |
| Enhanced PG synthesis | Frean et al., 1999 [22] | Equine articular cartilage; various HA doses | N/A | Yes |
| Fukuda et al., 1996 [56] | Bovine articular cartilage; various HA doses | N/A | Yes | |
| Enhanced PG synthesis in the presence of IL-1α | Stöve et al., 2002 [58] | Human chondrocytes from OA knee patients; HA, IL-1α or HA + IL-1α | N/A | N/A |
| Increased production of high-MW PGs | Kikuchi et al., 1996 [57] | Rabbit ligamental cells; various HA doses | N/A | Yes |
| Increased content and influenced distribution of PGs | Kikuchi et al., 2001 [108] | Rabbit chondrocytes; various HA concentrations | N/A | Yes |
| Suppressed PG release from cartilage | Yoshioka et al., 1997 [19] | Rabbit ACL transection; HA (five weekly injections) given 4 weeks PS | N/A | N/A |
| Larsen et al., 1992 [61] | Bovine cartilage explants; HA or hylan | N/A | N/A | |
| Suppressed PG release from cell matrix layer | Shimazu et al., 1993 [59] | Rabbit chondrocytes; various MWs and doses of HA | No | Yes |
| Decreased PG release from cartilage matrix | Morris et al., 1992 [60] | Bovine articular cartilage; various doses of HA with or without IL-1β | N/A | Yes |
| Prevented PG breakdown from cartilage | Ghosh et al., 1995 [53] | Ovine meniscectomy; HA (five weekly injections) given 16 weeks PS; keratan sulfate peptide measured in SF 1 week preinjection and 1 and 4 weeks postinjection | N/A | N/A |
| Protected extracellular matrix from degradation | Abatangelo et al., 1989 [63] | Canine ACL resection (Pond-Nuki); HA given 7 days PS weekly for 6 weeks | N/A | N/A |
ACL, anterior cruciate ligament; HA, hyaluronan (hyaluronic acid); IL, interleukin; MW, molecular weight; OA, osteoarthritis; PG, proteoglycan; PS, postsurgery; SF, synovial fluid.