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S100A8 and S100A9 in experimental osteoarthritis.

Zreiqat H, Belluoccio D, Smith MM, Wilson R, Rowley LA, Jones K, Ramaswamy Y, Vogl T, Roth J, Bateman JF, Little CB - Arthritis Res. Ther. (2010)

Bottom Line: The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR).Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased.In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tissue Engineering and Biomaterials Research Unit, School of AMME J07, Faculty of Engineering, Bosch Institute, University of Sydney, Corner of Shepherd and Cleavland Street, New South Wales 2006, Australia. hzreiqat@usyd.edu.au

ABSTRACT

Introduction: The objective was to evaluate the changes in S100A8 S100A9, and their complex (S100A8/S100A9) in cartilage during the onset of osteoarthritis (OA) as opposed to inflammatory arthritis.

Methods: S100A8 and S100A9 protein localization were determined in antigen-induced inflammatory arthritis in mice, mouse femoral head cartilage explants stimulated with interleukin-1 (IL-1), and in surgically-induced OA in mice. Microarray expression profiling of all S100 proteins in cartilage was evaluated at different times after initiation of degradation in femoral head explant cultures stimulated with IL-1 and surgically-induced OA. The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: Stimulation with IL-1 increased chondrocyte S100a8 and S100a9 mRNA and protein levels. There was increased chondrocyte mRNA expression of S100a8 and S100a9 in early but not late mouse OA. However, loss of the S100A8 staining in chondrocytes occurred as mouse OA progressed, in contrast to the positive reactivity for both S100A8 and S100A9 in chondrocytes in inflammatory arthritis in mice. Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased.

Conclusions: Chondrocyte derived S100A8 and S100A9 may have a sustained role in cartilage degradation in inflammatory arthritis. In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy.

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Fold change in S100 gene expression measured by microarray expression profiling, in micro-dissected cartilage from surgically-induced OA compared with sham-operated joints 1, 2 and 6 weeks post-operatively. Pooled samples were used from three sham or medial meniscal destabilization (MMD) joints per time point. *B-statistic ≥ 1.0. OA = osteoarthritis; po = post-operatively.
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Figure 4: Fold change in S100 gene expression measured by microarray expression profiling, in micro-dissected cartilage from surgically-induced OA compared with sham-operated joints 1, 2 and 6 weeks post-operatively. Pooled samples were used from three sham or medial meniscal destabilization (MMD) joints per time point. *B-statistic ≥ 1.0. OA = osteoarthritis; po = post-operatively.

Mentions: To determine whether the loss of S100A8 immunostaining in cartilage in OA was due to decreased expression, microarray mRNA expression profiling of the S100 protein family was performed [see Additional file 1]. The expression of all S100 genes in chondrocytes in the non-calcified articular cartilage at one, two and six weeks post-induction of OA was determined and results expressed as fold change compared with the sham-operated joints (Figure 4). The expression of a number of S100 mRNAs including S100a5, S100a6, S100a8, S100a9, S100a11, and S100b was significantly (B-statistic ≥ 1.0) regulated in chondrocytes following surgical induction of OA. The most highly regulated were S100a8 and S100a9, and, unlike other S100 family members, they showed differential regulation with 7- to 14-fold upregulation in early (week one and two) stages of OA and a 7- to 18-fold decrease compared with sham-operated levels in late-stage (week six) disease. The change in S100a8 and S100a9 expression measured using qRT-PCR showed some variability between the individual animals. Nevertheless, three of the four animals at each time point showed the same direction (i.e. increase or decrease) of change, and the median fold change (n = 4) had a similar temporal pattern to that observed in microarray analysis: 3.9- and 11-fold increase in S100a8 and S100a9, respectively, in early OA (two weeks), and a 16- and 25-fold decrease, respectively, in late-stage (six weeks) MMD-induced OA.


S100A8 and S100A9 in experimental osteoarthritis.

Zreiqat H, Belluoccio D, Smith MM, Wilson R, Rowley LA, Jones K, Ramaswamy Y, Vogl T, Roth J, Bateman JF, Little CB - Arthritis Res. Ther. (2010)

Fold change in S100 gene expression measured by microarray expression profiling, in micro-dissected cartilage from surgically-induced OA compared with sham-operated joints 1, 2 and 6 weeks post-operatively. Pooled samples were used from three sham or medial meniscal destabilization (MMD) joints per time point. *B-statistic ≥ 1.0. OA = osteoarthritis; po = post-operatively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875644&req=5

Figure 4: Fold change in S100 gene expression measured by microarray expression profiling, in micro-dissected cartilage from surgically-induced OA compared with sham-operated joints 1, 2 and 6 weeks post-operatively. Pooled samples were used from three sham or medial meniscal destabilization (MMD) joints per time point. *B-statistic ≥ 1.0. OA = osteoarthritis; po = post-operatively.
Mentions: To determine whether the loss of S100A8 immunostaining in cartilage in OA was due to decreased expression, microarray mRNA expression profiling of the S100 protein family was performed [see Additional file 1]. The expression of all S100 genes in chondrocytes in the non-calcified articular cartilage at one, two and six weeks post-induction of OA was determined and results expressed as fold change compared with the sham-operated joints (Figure 4). The expression of a number of S100 mRNAs including S100a5, S100a6, S100a8, S100a9, S100a11, and S100b was significantly (B-statistic ≥ 1.0) regulated in chondrocytes following surgical induction of OA. The most highly regulated were S100a8 and S100a9, and, unlike other S100 family members, they showed differential regulation with 7- to 14-fold upregulation in early (week one and two) stages of OA and a 7- to 18-fold decrease compared with sham-operated levels in late-stage (week six) disease. The change in S100a8 and S100a9 expression measured using qRT-PCR showed some variability between the individual animals. Nevertheless, three of the four animals at each time point showed the same direction (i.e. increase or decrease) of change, and the median fold change (n = 4) had a similar temporal pattern to that observed in microarray analysis: 3.9- and 11-fold increase in S100a8 and S100a9, respectively, in early OA (two weeks), and a 16- and 25-fold decrease, respectively, in late-stage (six weeks) MMD-induced OA.

Bottom Line: The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR).Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased.In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tissue Engineering and Biomaterials Research Unit, School of AMME J07, Faculty of Engineering, Bosch Institute, University of Sydney, Corner of Shepherd and Cleavland Street, New South Wales 2006, Australia. hzreiqat@usyd.edu.au

ABSTRACT

Introduction: The objective was to evaluate the changes in S100A8 S100A9, and their complex (S100A8/S100A9) in cartilage during the onset of osteoarthritis (OA) as opposed to inflammatory arthritis.

Methods: S100A8 and S100A9 protein localization were determined in antigen-induced inflammatory arthritis in mice, mouse femoral head cartilage explants stimulated with interleukin-1 (IL-1), and in surgically-induced OA in mice. Microarray expression profiling of all S100 proteins in cartilage was evaluated at different times after initiation of degradation in femoral head explant cultures stimulated with IL-1 and surgically-induced OA. The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: Stimulation with IL-1 increased chondrocyte S100a8 and S100a9 mRNA and protein levels. There was increased chondrocyte mRNA expression of S100a8 and S100a9 in early but not late mouse OA. However, loss of the S100A8 staining in chondrocytes occurred as mouse OA progressed, in contrast to the positive reactivity for both S100A8 and S100A9 in chondrocytes in inflammatory arthritis in mice. Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased.

Conclusions: Chondrocyte derived S100A8 and S100A9 may have a sustained role in cartilage degradation in inflammatory arthritis. In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy.

Show MeSH
Related in: MedlinePlus