Effects of TGF-β on Hyaluronan Anabolism in Fibroblasts Derived from the Synovial Membrane of the Rabbit Temporomandibular Joint

Tanimoto, Kotaro; Suzuki, Aya; Ohno, Shigeru; Honda, K.; Tanaka, Nobuaki; Doi, Takumi; Yoneno, Kiyoshi; Ohno-Nakahara, M.; Nakatani, Yuki; Ueki, M.; Tanne, Kazuo

doi:10.1177/154405910408300108

Cited by 33 publications

(26 citation statements)

References 29 publications

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“…In agreement with previous findings (17)(18)(19), TGF-␤1 increased the amount of HA in the culture media of normal, OA, and RA synovial fibroblasts (Fig. 9A).…”

Section: Correlation Of Tgf-␤ Receptor Type I and Ii Expression With supporting

confidence: 93%

“…TGF-␤1 is present at high levels in synovial fluids of OA and RA patients (17) and expected to act as an anabolic factor for HA production. However, our data provide evidence that the stimulation of arthritic synovial fibroblasts by TGF-␤1 fails in generation and accumulation of high molecular weight HA because of insufficient down-regulation of HYBID.…”

Section: Discussionmentioning

confidence: 99%

“…However, regulation mechanisms about the HYBID-mediated HA degradation by growth factors in skin fibroblasts remain elusive. Although TGF-␤1 is present at high levels in synovial fluids of patients with OA or RA (17) and is considered to act as a major stimulator of HA synthesis in arthritic synovial fibroblasts (18,19), no information is available for the expression of HYBID and HAS genes or HA species synthesized under stimulation with TGF-␤1.…”

mentioning

confidence: 99%

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Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts

Nagaoka¹,

Yoshida²,

Nakamura³

et al. 2015

Journal of Biological Chemistry

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Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-␤1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-␤1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-␤1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-␤1 upregulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-␤1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-␤1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient downregulation of HYBID by TGF-␤1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. Hyaluronan (HA)3 is a nonsulfated linear glycosaminoglycan composed of repeating disaccharide units of ␤-(1,3)-linked-Dglucuronic acid and ␤-(1,4)-linked-N-acetyl-D-glucosamine. HA is ubiquitously present as a major component in vertebrate connective tissues such as skin and synovial membrane and contributes to space filling, lubrication, and cell proliferation and migration (1). The turnover of HA in most tissues is extraordinarily rapid; the half-life of HA in the skin, which contains about half of all HA in the body, is 1-1.5 days (2). Thus, the tight control of HA synthesis and degradation is necessary for this turnover and seems to finely balance the amounts of high molecular mass HA (1,000 -10,000 kDa) within tissues (1, 2). On the other hand, an imbalance of synthesis and degradation causes the accumulation of HA with different molecular weights, which is commonly observed in diseases such as arthritis and cancers (3-5). Synovial fluids from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) contain lower molecular mass HA (as low as 200 kDa) than that from normal subjects, leading to decreased synovial viscosity and increased inflammatory responses (6). HA is synthesized by HA synthases (Has1, Has2, and Has3) at the cell membrane, and the expression of Has enzyme...

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“…In agreement with previous findings (17)(18)(19), TGF-␤1 increased the amount of HA in the culture media of normal, OA, and RA synovial fibroblasts (Fig. 9A).…”

Section: Correlation Of Tgf-␤ Receptor Type I and Ii Expression With supporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts

Nagaoka¹,

Yoshida²,

Nakamura³

et al. 2015

Journal of Biological Chemistry

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show abstract

“…28 Briefly, the medium was moved to extraction columns (Bond Elut SCX and BondElut SAX; GL Sciences, Tokyo, Japan). After washing, the solvents were eluted by 3 mL of 50 mM MeOH/HCl.…”

Section: Quantification Of Ha Concentration In the Culturementioning

confidence: 99%

Modulation of Hyaluronan Fragmentation by Interleukin-1 Beta in Synovial Membrane Cells

et al. 2010

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Hyaluronan (HA) plays a crucial role in the lubricating and buffering properties of synovial fluid. The purpose of this study was to examine the effects of interleukin (IL)-1beta on HA degradation in cultured synovial membrane cells. The rabbit synovial membrane cell line HIG-82 was cultured with and without IL-1beta. The amounts of HA of varying molecular weights in the medium were analyzed using high-performance liquid chromatography, the mRNA levels of HA synthase (HAS) and hyaluronidase (HYAL) were analyzed by means of real-time PCR, and HYAL activity was analyzed by HA zymography. The amounts of HA with a molecular weight lower than 300 kDa, and between 300 and 1900 kDa, in the culture medium of HIG-82 cells were significantly higher in the presence of IL-1beta. However, the amount of HA with a molecular weight greater than 1900 kDa was significantly lower in the presence of IL-1beta. Both HAS2 and HAS3 mRNA levels were upregulated by treatment with IL-1beta. So, too, were the levels of HYAL1 and HYAL2 mRNA, which resulted in enhanced HYAL activity. However, HYAL activity was inhibited by transfection of HYAL2-siRNA. Our results suggest that IL-1beta is a crucial factor in the fragmentation of HA in inflammatory joints.

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“…It is synthesized by three HA synthase isoforms (HAS1-3), located at the inner surface of the cell membrane. TGF-␤ is known as a potent inducer of HA synthesis in synovial and lung fibroblast (50,51). For this purpose, HDF were stimulated with TGF-␤, Bt 2 cAMP, TGF-␤ plus Bt 2 cAMP, or were left untreated.…”

Section: Camp Does Not Antagonize But Synergizes With Tgf-␤ To Enhancementioning

confidence: 99%

Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

Schiller

Dennler

Anderegg

et al. 2010

Journal of Biological Chemistry

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Effects of TGF-β on Hyaluronan Anabolism in Fibroblasts Derived from the Synovial Membrane of the Rabbit Temporomandibular Joint

Cited by 33 publications

References 29 publications

Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts

Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts

Modulation of Hyaluronan Fragmentation by Interleukin-1 Beta in Synovial Membrane Cells

Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

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