The effect of hyaluronan on CD44-mediated survival of normal and hydroxyl radical-damaged chondrocytes

Brun, Paola; Panfilo, Susi; Gordini, D. Daga; Cortivo, Roberta; Abatangelo, Giovanni

doi:10.1016/s1063-4584(02)00352-7

Cited by 42 publications

(38 citation statements)

References 47 publications

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“…In vitro studies have shown that HA has chondroprotective [34], and anti-inflammatory and structure-modifying effects in synoviocytes through down-regulation of gene expression for various cytokines, aggrecanase-2 and other enzymes [35]; effects thought to occur via CD44-mediated metabolic modulation [34][35][36]. In addition, the enduring clinical efficacy (months) of intra-articular HA compared with its relatively short half-life may also be accounted for by CD44-mediated metabolic modulation.…”

Section: Molecular Weightmentioning

confidence: 99%

The role of intra-articular hyaluronan (Sinovial®) in the treatment of osteoarthritis

2010

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Osteoarthritis (OA) leads to significant pain and disability. For pain relief, a tailored approach using non-pharmacological and pharmacological therapies is recommended. If adequate symptom relief is not achieved with acetaminophen, other pharmacological options include non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, intra-articular corticosteroids and intra-articular hyaluronic acid (HA) viscosupplementation. Most of these therapies generally do not improve functional ability or quality of life or are associated with tolerability concerns. In OA patients, concentration and molecular weight (MW) of HA are reduced, diminishing elastoviscosity of the synovial fluid, joint lubrication and shock absorbancy, and possibly anti-inflammatory, analgesic and chondroprotective effects. In knee OA, viscosupplementation with 3-5 weekly intra-articular HA injections diminishes pain and improves disability, generally within 1 week and for up to 3-6 months and is well tolerated. HAs have comparable efficacy as NSAIDs, with less gastrointestinal adverse events, and compared with intra-articular corticosteroids, benefits last generally longer. High MW hylans provide comparable benefits versus HA, albeit with an increased risk of immunogenic adverse events. In mild-to-moderate hip OA, intra-articular injection of HA moderately improved pain and function, generally for up to 3 months with no serious adverse events. Efficacy in other joints is being evaluated. Viscosupplementation with intra-articular Sinovial(®) (other trade names: Yaral(®), Intragel(®)) injections (an HA of low-medium MW) relieves pain and improves function in OA of the knee, and other joints including the carpometacarpal joint of the thumb and the shoulder. HA viscosupplementation, including use of Sinovial(®), is a valuable treatment approach for OA patients, if other therapies are contraindicated or have failed.

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Section: Molecular Weightmentioning

confidence: 99%

The role of intra-articular hyaluronan (Sinovial®) in the treatment of osteoarthritis

2010

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“…Previous studies have shown the involvement of CD44 in the HA effects 20 21 44. No previous studies have clarified the intracellular signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic chondrocytes

Yatabe

Mochizuki

Takizawa

et al. 2008

Annals of the Rheumatic Diseases

148

111

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Background:Intra-articular injection of hyaluronan (HA) has been suggested to have a disease-modifying effect in osteoarthritis, but little is known about the possible mechanisms.Objective:To investigate the effects of HA species of different molecular mass, including 800 kDa (HA800) and 2700 kDa (HA2700), on the expression of aggrecanases (ie, ADAMTS species), which play a key role in aggrecan degradation.Methods:The effects of HA species on the expression of ADAMTS1, 4, 5, 8, 9 and 15 in interleukin 1α (IL1α)-stimulated osteoarthritic chondrocytes were studied by reverse transcription PCR and real-time PCR. Expression of ADAMTS4 protein and aggrecanase activity and signal transduction pathways of IL1, CD44 and intracellular adhesion molecule 1 (ICAM1) were examined by immunoblotting.Results:IL1α treatment of chondrocytes induced ADAMTS4, and HA800 and HA2700 significantly decreased IL1α-induced expression of ADAMTS4 mRNA and protein. IL1α-stimulated aggrecanase activity in osteoarthritic chondrocytes was reduced by treatment with HA2700 or transfection of small interfering RNA for ADAMTS4. A similar result was obtained when HA2700 was added to explant cultures of osteoarthritic cartilage. HA2700 neither directly inhibited nor bound to ADAMTS4. Downregulation of ADAMTS4 expression by HA2700 was attenuated by treatment of IL1α-treated chondrocytes with antibodies to CD44 and/or ICAM1. The increased phosphorylation of IL1 receptor-associated kinase-1 and extracellular signal-regulated protein kinase1/2 induced by the IL1α treatment was downregulated by enhanced IRAK-M expression after HA2700 treatment.Conclusion:These data suggest that HA2700 suppresses aggrecan degradation by downregulating IL1α-induced ADAMTS4 expression through the CD44 and ICAM1 signalling pathways in osteoarthritic chondrocytes.

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“…The regional loss of HA coincides with the regional upregulation of CD44 (16). Exogenous HA exerts antiapoptotic effects on chondrocytes by binding to specific receptors, including CD44 (17,18).…”

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confidence: 82%

Increase in the expression of the transmembrane surface receptor CD44v6 on chondrocytes in animals with osteoarthritis

Tibesku¹,

Szuwart²,

Ocken³

et al. 2005

Arthritis & Rheumatism

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Objective. To evaluate the expression of CD44v6 on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA).Methods. In 12 NZW rabbits, the anterior cruciate ligament (ACL) was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load-bearing area was evaluated histologically according to the Mankin scale and by immunostaining for CD44v6.Results. There was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed constant expression of CD44v6 in the control group. In the experimental group, a positive linear correlation between CD44v6 expression and macroscopic and histologic grades was found.Conclusion. The results show an in vivo increase in the expression of the hyaluronan receptor CD44 over the time course of OA. Further studies are needed to evaluate whether this pattern applies to humans and whether new treatment approaches could evolve from this knowledge.

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The effect of hyaluronan on CD44-mediated survival of normal and hydroxyl radical-damaged chondrocytes

Abstract: HA (0.5 mg/ml of 5-7 x 10(5)) significantly increased the viability of normal human chondrocytes in primary culture and restored cell viability to near normal levels after oxidative cell injury.

Cited by 42 publications

References 47 publications

The role of intra-articular hyaluronan (Sinovial®) in the treatment of osteoarthritis

The role of intra-articular hyaluronan (Sinovial®) in the treatment of osteoarthritis

Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic chondrocytes

Increase in the expression of the transmembrane surface receptor CD44v6 on chondrocytes in animals with osteoarthritis

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