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Table 5 Effects of hyaluronan (hyaluronic acid) and hylans on cartilage

From: Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action

Effect

Reference

Experimental model/treatment/endpoints

MW-dependent

Suppressed cartilage degeneration

Shimizu et al., 1998 [18]

Rabbit ACL transection; HA (five weekly injections) or crosslinked HA (three weekly injections) 4 weeks PS; observations 9 weeks PS

Yes

 

Listrat et al., 1997 [10]

Clinical study of OA patient (n = 36; 1 year); three weekly HA injections every 3 months; arthroscopic evaluation 1 year from study start

N/A

Prevented cartilage damage

Ghosh et al., 1995 [53]

Ovine meniscectomy; HA (five weekly injections) given 16 weeks PS; joint articular cartilage histologically graded 5 weeks after last injection

N/A

Prevented cartilage damage; maintained normal morphology

Schiavinato et al., 1989 [20]

Pond-Nuki canine OA model; HA given 1–7 weeks PS or 7–17 weeks PS; observations 7, 13, and 17 weeks PS

N/A

Preserved cartilage histology and smoothness

Yoshimi et al., 1994 [102]

Rabbit ACL resection; HA (various MWs) injections one week PS weekly until assessments were made (6 or 12 weeks)

Yes

 

Sakakibara et al., 1994 [103]

Rabbits immobilized at the onset of HA administration; HA (various MWs) twice/week for 5 weeks; observations 1–6 weeks after immobilization

Yes

 

Fu et al., 2001 [94]

Immobilization-induced cartilage degradation in rabbits; six weekly injections of HA with remobilization; assessments 1 week after the last injection

Yes

Improved superficial cartilage layer and synovial membrane morphology; reduced synovial thickness and inflammation

Frizziero et al., 1998 [104]

Clinical study of OA patients (n = 40); HA (five weekly injections); cartilage and synovial biopsies and arthroscopy performed at baseline and 6 months after first injection

N/A

Improved synovium structure and synoviocyte morphology; reduced inflammatory cells in the synovium

Pasquali Ronchetti et al., 2001 [105]

Clinical study of patients with primary and secondary OA (n = 99); HA (five weekly injections) or MP (three weekly injections); synovial biopsies 2–3 weeks pretreatment and 6 months post-treatment

N/A

Improved superficial cartilage compactness and thickness; increased chondrocyte density (HA better results than MP for most parameters); improved chondrocyte morphology

Guidolin et al., 2001 [106]

Clinical study of OA patients (n = 24); HA (five weekly injections) or MP (three weekly injections); biopsies taken 6 months from treatment initiation

N/A

Prevented cartilage damage; maintained cartilage thickness, area, and smoothness

Yoshioka et al., 1997 [19]

Rabbit ACL transection; HA given 4 weeks PS; assessed femoral condyles 9 weeks after surgery

N/A

Prevented cartilage damage; maintained cartilage thickness, area, smoothness, and surface uniformity

Shimizu et al., 1998 [95]

Rabbit ACL transection; HA given 4 weeks PS; assessed femoral condyles 21 weeks after surgery

N/A

Maintained cartilage smoothness; prevented deep fissures and cracks in the cartilage surface

Wenz et al., 2000 [101]

Severe and resect canine ACL (Pond-Nuki); HA (five weekly injections) given 3, 6, or 12 weeks PS; assessed patella and patella/knee 5 weeks after last injection

N/A

Enhanced meniscal regeneration; inhibited cartilage deterioration

Kobayashi et al., 2000 [96]

Rabbit partial meniscectomy; HA (five weekly injections) 1 week PS; assessed meniscus and tibial cartilage 6 months PS

N/A

Reduced disease severity

Marshall et al., 2000 [99]

Canine OA models; hylan G-F 20 (three weekly injections) given 2 months PS; assessed 6 months after treatment

N/A

Accelerated migration of synovial cells; enhanced migration of chondrocytes when coincubated with bFGF

Maniwa et al., 2001 [107]

Rabbit synovial cells and chondrocytes incubated with HA, bFGF, HA + bFGF

N/A

  1. ACL, anterior cruciate ligament; bFGF, basic fibroblastic growth factor; HA, hyaluronan (hyaluronic acid); MP, methylprednisolone; MW, molecular weight; OA, osteoarthritis; PS, postsurgery.