Age-Related Effects of TGF-β on Proteoglycan Synthesis in Equine Articular Cartilage

Iqbal, Javed; Dudhia, Jayesh; Bird, James; Bayliss, Michael T.

doi:10.1006/bbrc.2000.3167

Cited by 50 publications

(37 citation statements)

References 25 publications

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“…25 This may be partly explained by the fact that we used cells from relatively old donors who were age-matched with the patients, because TGF-β1 expression was shown to decrease with aging in normal cells. 26,27 To determine the possible mechanism of inhibitory action of HGF on collagen production, we examined the effect of HGF on the expression of several cytokines related to collagen metabolism. The results showed that HGF treatment for 48 h suppressed CTGF but not TGF-β1 expression in SSc cells.…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic effects of hepatocyte growth factor on scleroderma fibroblasts and analysis of its mechanism

Sherriff-Tadano

Ohta²,

Morito

et al. 2006

Mod Rheumatol

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We investigated the effect of hepatocyte growth factor (HGF) on collagen metabolism in cultured fibroblasts from scleroderma (SSc) patients and discussed the possible mechanism of its effect. Synthesis of matrix metalloproteinase-1 (MMP-1) and collagen and mRNA levels of various cytokines were examined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively. Hepatocyte growth factor enhanced MMP-1 production and mRNA levels of MMP-1 and Ets-1 (a transcriptional factor of MMPs). In addition, HGF suppressed collagen synthesis and mRNA levels of procollagenalpha1(I) and connective tissue growth factor (CTGF) in SSc fibroblasts. Expression of transforming growth factor (TGF)-beta1 was not inhibited significantly in SSc or control fibroblasts. Hepatocyte growth factor also increased interferon (IFN)-gamma mRNA significantly in SSc and control fibroblasts. Addition of anti-HGF antibody neutralized these effects of HGF on MMP-1 and collagen synthesis. The results suggest that HGF can suppress collagen accumulation in SSc fibroblasts by increasing MMP-1 levels possibly via activation of Ets-1 and also by decreasing collagen synthesis, which may be partly related to inhibition of CTGF, and increasing IFN-gamma levels rather than the effect on TGF-beta1. The present study indicates that HGF may be a promising therapeutic agent for this intractable disease.

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Section: Discussionmentioning

confidence: 99%

Antifibrotic effects of hepatocyte growth factor on scleroderma fibroblasts and analysis of its mechanism

Sherriff-Tadano

Ohta²,

Morito

et al. 2006

Mod Rheumatol

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“…The levels of IGF-I in serum and of TGF-β1 in cartilage are low in a neonate and rise during post-natal growth (Clemmons and Van Wyk 1984;Moroco et al 1997;Fortier et al 2005). IGF-I, TGF-β1, and BMP-7 continue to be expressed in immature and adult articular cartilages (Ellingsworth et al 1986;Luyten et al 1988;Schneiderman et al 1995;Fukumura et al 1998;Anderson et al 2000;Chubinskaya et al 2000;Iqbal et al 2000;Muehleman et al 2002) and reach concentrations of 1-50 ng/g cartilage tissue (Luyten et al 1988;Schneiderman et al 1995), 0.02-0.2 ng/ml synovial fluid (Wei and Messner 1998), 1-20 ng/g cartilage tissue (Chubinskaya et al 2002), respectively. Pathological cartilage/bone growth, such as that seen during the formation of osteophytes, also involves activities of growth factors such as TGF-β and PDGF (Horner et al 1996(Horner et al , 1998.…”

Section: Introductionmentioning

confidence: 99%

Regulation of immature cartilage growth by IGF-I, TGF-β1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network

Asanbaeva

Masuda

Thonar

et al. 2007

Biomech Model Mechanobiol

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Cartilage growth may involve alterations in the balance between the swelling tendency of proteoglycans and the restraining function of the collagen network. Growth factors, including IGF-I, TGF-beta1, BMP-7, and PDGF-AB, regulate chondrocyte metabolism and, consequently, may regulate cartilage growth. Immature bovine articular cartilage explants from the superficial and middle zones were incubated for 13 days in basal medium or medium supplemented with serum, IGF-I, TGF-beta1, BMP-7, or PDGF-AB. Variations in tissue size, accumulation of proteoglycan and collagen, and tensile properties were assessed. The inclusion of serum, IGF-I, or BMP-7 resulted in expansive tissue growth, stimulation of proteoglycan deposition but not of collagen, and a diminution of tensile integrity. The regulation of cartilage metabolism by TGF-beta1 resulted in tissue homeostasis, with maintenance of size, composition, and function. Incubation in basal medium or with PDGF-AB resulted in small volumetric and compositional changes, but a marked decrease in tensile integrity. These results demonstrate that the phenotype of cartilage growth, and the associated balance between proteoglycan content and integrity of the collagen network, is regulated differentially by certain growth factors.

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“…Chondrocytes number in cartilage significantly decrease with advancing age (Bobacz et al 2004), their proliferative response to serum changes and declines (Guerne et al 1995, Barbero et al 2004, cells senesce and shorten their telomere length (Martin and Buckwalter 2003). In horses, proteoglycan synthesis and chondrocyte responsiveness to TGFβ1 steadily decreases with increasing age (Iqbal et al 2000].…”

Section: Discussionmentioning

confidence: 99%

Influence of culture conditions on expansion and re-differentiation of chondrocytes from horses of different ages

Werren¹,

Diaz-Romero²,

Brehm³

et al. 2008

PHK

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SummaryTo evaluate the influence of types of sera and the donors age on proliferation and re-differentiation capacities of equine chondrocytes, cartilage tissue from 10 horses was obtained in the age range 2.5 to 19 years. Chondrocytes were isolated from the fetlock-joints and expanded in media containing different types of sera: fetal calf serum (FCS), fetal equine serum (FES), adult equine serum (AES) and autologous serum. Cells were expanded in monolayers at low and high seeding densities. Chondrocytes re-differentiation capacities were assessed in micromass pellet cultures after 4 weeks of incubation in chondrogenic medium supplemented with or without 5ng/ml TGFβ1. The neocartilagineous tissue formation was evaluated through proteoglycan and collagen type II deposition, and Berne score visual evaluation system. Results showed that the low seeding density allows for higher proliferation rates in FCS, FES and AES. In addition chondrocytes from younger horses proliferate faster independently of the serum type. Re-differentiation capacities are influenced by the animals age, type of serum during expansion, and the presence of TGFβ1 in pellet cultures. Cells from young horses appear to produce better neocartilage upon expansion in autologous serum, while cells from older horses re-differentiated better upon expansion in FCS. The expansion conditions of potential clinical relevance include the correct choice of sera according to the age of horse during monolayer culture for better subsequent re-differentiation and lower seeding densities allowing for smaller biopsy sampling and therefore less injury to the donor site.

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Age-Related Effects of TGF-β on Proteoglycan Synthesis in Equine Articular Cartilage

Cited by 50 publications

References 25 publications

Antifibrotic effects of hepatocyte growth factor on scleroderma fibroblasts and analysis of its mechanism

Antifibrotic effects of hepatocyte growth factor on scleroderma fibroblasts and analysis of its mechanism

Regulation of immature cartilage growth by IGF-I, TGF-β1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network

Influence of culture conditions on expansion and re-differentiation of chondrocytes from horses of different ages

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