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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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Histopathological examination of osteoarthritic changes in mouse knee (femoro-tibial) joints following medial meniscal destabilization (MMD). (a) Progressive cartilage damage at 2, 4, 8 and 16 weeks following medial meniscal destabilization-induced osteoarthritis (OA) in mouse knee joints. Toluidine blue/fast green stained paraffin sections. Scale bar = 200 μm. (b) Serial sections stained with toluidine blue or with S100A8 immunolocalization in mouse knees at different times following medial meniscal destabilization (MMD) or sham surgery (at 16 weeks). Scale bar = 100 μm. Negative control sections were immunostained using an equivalent concentration of rabbit IgG.
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Figure 2: Histopathological examination of osteoarthritic changes in mouse knee (femoro-tibial) joints following medial meniscal destabilization (MMD). (a) Progressive cartilage damage at 2, 4, 8 and 16 weeks following medial meniscal destabilization-induced osteoarthritis (OA) in mouse knee joints. Toluidine blue/fast green stained paraffin sections. Scale bar = 200 μm. (b) Serial sections stained with toluidine blue or with S100A8 immunolocalization in mouse knees at different times following medial meniscal destabilization (MMD) or sham surgery (at 16 weeks). Scale bar = 100 μm. Negative control sections were immunostained using an equivalent concentration of rabbit IgG.

Mentions: Meniscal destabilization induced a progressive deterioration of the articular cartilage in the medial femoro-tibial joint (Figure 2a) with no evidence of synovial inflammation as previously described [16]. Cartilage damage at two weeks was characterized by a focal loss of proteoglycan from the non-calcified cartilage in the central weight-bearing region of the tibial plateau but no structural damage. The area of proteoglycan loss expanded with time and at eight weeks was accompanied by evidence of surface fibrillation and some areas of erosion. By 16 weeks there was full thickness erosion of non-calcified cartilage to cover over 50% of the joint surface.


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)

Histopathological examination of osteoarthritic changes in mouse knee (femoro-tibial) joints following medial meniscal destabilization (MMD). (a) Progressive cartilage damage at 2, 4, 8 and 16 weeks following medial meniscal destabilization-induced osteoarthritis (OA) in mouse knee joints. Toluidine blue/fast green stained paraffin sections. Scale bar = 200 μm. (b) Serial sections stained with toluidine blue or with S100A8 immunolocalization in mouse knees at different times following medial meniscal destabilization (MMD) or sham surgery (at 16 weeks). Scale bar = 100 μm. Negative control sections were immunostained using an equivalent concentration of rabbit IgG.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Histopathological examination of osteoarthritic changes in mouse knee (femoro-tibial) joints following medial meniscal destabilization (MMD). (a) Progressive cartilage damage at 2, 4, 8 and 16 weeks following medial meniscal destabilization-induced osteoarthritis (OA) in mouse knee joints. Toluidine blue/fast green stained paraffin sections. Scale bar = 200 μm. (b) Serial sections stained with toluidine blue or with S100A8 immunolocalization in mouse knees at different times following medial meniscal destabilization (MMD) or sham surgery (at 16 weeks). Scale bar = 100 μm. Negative control sections were immunostained using an equivalent concentration of rabbit IgG.
Mentions: Meniscal destabilization induced a progressive deterioration of the articular cartilage in the medial femoro-tibial joint (Figure 2a) with no evidence of synovial inflammation as previously described [16]. Cartilage damage at two weeks was characterized by a focal loss of proteoglycan from the non-calcified cartilage in the central weight-bearing region of the tibial plateau but no structural damage. The area of proteoglycan loss expanded with time and at eight weeks was accompanied by evidence of surface fibrillation and some areas of erosion. By 16 weeks there was full thickness erosion of non-calcified cartilage to cover over 50% of the joint surface.

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