Molecular Weight-Dependent Effects of Hyaluronate on the Arthritic Synovium.

Asari, Akira; Miyauchi, Satoshi; Matsuzaka, S.; Ito, Tomomi; Kominami, Eiki; Uchiyama, Yasuo

doi:10.1679/aohc.61.125

Cited by 83 publications

(51 citation statements)

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“…It is well known that brief ischemia induces tolerance to subsequent ischemia in hippocampal neurons as a result of the induction of Hsp70 expression (5). We have previously shown that intraarticular treatment with hyaluronan (HA) preparation (840 kDa), HA84, suppresses degeneration of synovial cells in a canine arthritis model and up-regulates Hsp72 expression (6,7). In that study, we also injected fluorescent-labeled HA84 in synovial tissues and found that some labeled HA particles could not be detected by means of an HA-binding protein that binds specifically to HA molecules larger than decasaccharides (7).…”

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confidence: 99%

Effect of Hyaluronan Oligosaccharides on the Expression of Heat Shock Protein 72

Xu¹,

Ito²,

Tawada³

et al. 2002

Journal of Biological Chemistry

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109

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We have previously shown that intraarticular treatment with a hyaluronan (HA) preparation (840 kDa), HA84, up-regulates heat shock protein 72 (Hsp72) expression and suppresses degeneration of synovial cells in an arthritis model. In that study, the HA84 administered was degraded into HA oligosaccharides in the synovial tissue, suggesting that HA84 or degradation products of HA may up-regulate Hsp72 expression. Thus, in the present study, we examined the effects of HA of various molecular sizes on Hsp72 expression and cell death in stressed cells. Western blotting analysis showed that treatment of K562 cells with HA tetrasaccharides up-regulated Hsp72 expression after exposure to hyperthermia. On the other hand, treatment of the cells with HA of other sizes (di-, hexa-, deca-, dodecasaccharides), HA84, or tetrasaccharides of keratan sulfate did not elicit any change in expression of the Hsp72 protein. Treatment of the cells with tetrasaccharides of HA up-regulated not only expression of the Hsp72 protein but also Hsp72 mRNA expression and enhanced activation of HSF1, a transcription factor controlling Hsp72 expression, after exposure to hyperthermia. Because the level of Hsp72 protein was not affected by tetrasaccharides of HA when the K562 cells were kept at 37°C without any stress, it is evident that tetrasaccharides of HA did not act as a stress factor. In addition, tetrasaccharides of HA suppressed cell death in the case of K562 cells exposed to hyperthermia and of PC12 cells under serum deprivation. These results suggest that a certain size of oligosaccharides, i.e. the tetrasaccharides of HA, up-regulates Hsp72 expression by enhancing the activation of HSF1 under stress conditions and suppresses cell death.Heat shock proteins (Hsps) 1 are induced to suppress cell damage when cells are exposed to environmental insult (1, 2).Hsp70 suppresses apoptosis by preventing processing of caspase 3 (3, 4). It is well known that brief ischemia induces tolerance to subsequent ischemia in hippocampal neurons as a result of the induction of Hsp70 expression (5). We have previously shown that intraarticular treatment with hyaluronan (HA) preparation (840 kDa), HA84, suppresses degeneration of synovial cells in a canine arthritis model and up-regulates Hsp72 expression (6, 7). In that study, we also injected fluorescent-labeled HA84 in synovial tissues and found that some labeled HA particles could not be detected by means of an HA-binding protein that binds specifically to HA molecules larger than decasaccharides (7). These observations suggested that HA oligosaccharides formed through degradation of HA84 in the tissue might suppress cell damage by up-regulating Hsp72 expression. In the present study, we prepared HA oligosaccharides of various molecular sizes and treated cultured cells with them under stress conditions in an effort to understand the appropriate size of HA oligosaccharides required to up-regulate Hsp72 expression or to suppress cell death. Effects of HA molecules on Hsp72 were investigated by examining bot...

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confidence: 99%

Effect of Hyaluronan Oligosaccharides on the Expression of Heat Shock Protein 72

Xu¹,

Ito²,

Tawada³

et al. 2002

Journal of Biological Chemistry

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109

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“…Alguns não mostraram diferença estatística (15) , enquanto outros, maior eficácia do composto com alto peso molecular (16)(17)(18) e outros ainda, maior eficácia do composto de baixo peso molecular (11,19,20) . Outro estudo ainda mostrou similaridade entre o tratamento com ácido hialurônico e o tratamento apenas com medidas físicas/fisioterapia (18) .…”

Section: áCido Hialurônicounclassified

Tratamento medicamentoso da osteoartrose do joelho

Rezende¹,

Gobbi²

2009

Rev. bras. ortop.

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RESUMOO tratamento clínico da osteoartrite/artrose (OA) está sempre indicado e baseia-se no autocuidado feito pelo paciente e orientado pelo médico. O uso de medicamentos é complementar às medidas de emagrecimento, ganho de força, de propriocepção, de flexibilidade e de amplitude de movimento. Entre os medicamentos disponíveis para o tratamento da OA há os que são essencialmente analgésicos e que não interferem no curso da doença; bem como os anti-inflamatórios, controversos por seus efeitos colaterais e pelo seu papel na OA, porém, com propriedades analgésicas e anti-inflamatórias indiscutíveis; e, por fim, as drogas modificadoras de estrutura, que retardam a evolução da OA. As medicações ainda podem ser de uso tópico, intra-articular, oral e injetável (sistêmico). As várias apresentações de ácido hialurônico (AH) mostram o poder analgésico da droga e há indícios de poder modificador de estrutura da cartilagem pela medicação. Há nível de evidência IA, para diacereína e para a glucosamina, de que retardam a evolução da OA. Mais tecnologia para diagnóstico e controle de tratamento da OA, bem como mais estudos multicêntricos são necessários para consolidar o poder do tratamento medicamentoso de outras drogas. Declaramos existência de conflitos de interesse com Aché, Genzyme, Merck do Brasil, Solvay, TRB Pharma, Zambon, Zodiac. Neste artigo, não favorecemos nenhum produto comercial. Todas as informações são baseadas em literatura médica e não houve nenhuma forma de patrocínio para realização deste artigo pelas empresas responsáveis pelas medicações citadas. Descritores -

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“…It is found in the extracellular matrix of several connective tissues, including joint cartilage and synovial fluid [11][12][13] . In such sites, HA molecules are predominantly synthesized by type B synovial cells [12][13][14][15] . Metabolic HA activity in cell renewal helps the nutrition of avascular zones of the disk and joint cartilage through its combination with glycosaminoglycans coming from proteoglycans produced by condrocytes.…”

Section: Introductionmentioning

confidence: 99%

“…The use of this product according to its molecular weight may increase the production of natural HA by synovial cells, improve or normalize jaw functions as from the release of adhesion zones between the mandibular fossa and the joint disk 23 . HA properties are predominantly explored in the context of viscosuplementation, but it is worth stressing that very high molecular weight molecules (between 1 and 6 x 10 6 Da) are prevented from passing from the intra-articular to the intercellular medium, thus being unable to act on synoviocytes and chondrocytes, which would be needed to decrease synovial inflammation and restore natural synovial fluid properties, which has been called "viscoinduction" 14,15 . According to this theory [13][14][15] , products with molecular weight between 0.5 and 1 x 10 6 Da would provide better effects in vivo 23 and could promote endogenous HA synthesis by synoviocytes 14,15 .…”

Section: Introductionmentioning

confidence: 99%

“…HA properties are predominantly explored in the context of viscosuplementation, but it is worth stressing that very high molecular weight molecules (between 1 and 6 x 10 6 Da) are prevented from passing from the intra-articular to the intercellular medium, thus being unable to act on synoviocytes and chondrocytes, which would be needed to decrease synovial inflammation and restore natural synovial fluid properties, which has been called "viscoinduction" 14,15 . According to this theory [13][14][15] , products with molecular weight between 0.5 and 1 x 10 6 Da would provide better effects in vivo 23 and could promote endogenous HA synthesis by synoviocytes 14,15 . In the same line, other researchers 24 have established an even narrower molecular weight range (500-730 kDa) as that able to act on synovial fibroblasts, restoring their ability to synthesize HA 13 .…”

Section: Introductionmentioning

confidence: 99%

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