Limits...
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.

Show MeSH

Related in: MedlinePlus

S100A8 and S100A9 immunostaining in cartilage and subchondral bone at the joint margins following sham operation or medial meniscal destabilization at 4 and 16 weeks. Scale bar = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2875644&req=5

Figure 3: S100A8 and S100A9 immunostaining in cartilage and subchondral bone at the joint margins following sham operation or medial meniscal destabilization at 4 and 16 weeks. Scale bar = 100 μm.

Mentions: There was no difference in immunostaining for S100A8 and S100A9 between non-operated and sham-operated joints at any time (results not shown) and therefore only sham-operated results are included (Figure 2b). As described in saline-injected joints above, chondrocytes throughout the non-calcified cartilage in non-operated and sham-operated joints showed positive staining for S100A8 (Figure 2b) but not S100A9 (not shown). In marked contrast to the AIA model, with induction of OA there was a loss of chondrocyte S100A8 immunoreactivity in the non-calcified cartilage compared with the corresponding sham-operated joint (Figure 2b). The loss of S100A8 chondrocyte staining extended beyond the area of proteoglycan loss defined by decreased toluidine blue staining. Even at late stages of OA with extensive cartilage erosion, chondrocytes in the remaining intact cartilage in the load-bearing region of the joint had reduced or lost S100A8 reactivity (Figure 2b, week 8 and 16). However, S100A8 reactivity was still apparent in chondrocytes at the joint margins at all time points, and in the calcified cartilage, bone marrow and bone of developing and mature osteophytes (Figure 3). In contrast, chondrocytes showed little positive S100A9 immunostaining in marginal regions in either normal (non-operated or sham-operated) or OA joints, although bone marrow and some osteocytes were positive (Figure 3).


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)

S100A8 and S100A9 immunostaining in cartilage and subchondral bone at the joint margins following sham operation or medial meniscal destabilization at 4 and 16 weeks. Scale bar = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: S100A8 and S100A9 immunostaining in cartilage and subchondral bone at the joint margins following sham operation or medial meniscal destabilization at 4 and 16 weeks. Scale bar = 100 μm.
Mentions: There was no difference in immunostaining for S100A8 and S100A9 between non-operated and sham-operated joints at any time (results not shown) and therefore only sham-operated results are included (Figure 2b). As described in saline-injected joints above, chondrocytes throughout the non-calcified cartilage in non-operated and sham-operated joints showed positive staining for S100A8 (Figure 2b) but not S100A9 (not shown). In marked contrast to the AIA model, with induction of OA there was a loss of chondrocyte S100A8 immunoreactivity in the non-calcified cartilage compared with the corresponding sham-operated joint (Figure 2b). The loss of S100A8 chondrocyte staining extended beyond the area of proteoglycan loss defined by decreased toluidine blue staining. Even at late stages of OA with extensive cartilage erosion, chondrocytes in the remaining intact cartilage in the load-bearing region of the joint had reduced or lost S100A8 reactivity (Figure 2b, week 8 and 16). However, S100A8 reactivity was still apparent in chondrocytes at the joint margins at all time points, and in the calcified cartilage, bone marrow and bone of developing and mature osteophytes (Figure 3). In contrast, chondrocytes showed little positive S100A9 immunostaining in marginal regions in either normal (non-operated or sham-operated) or OA joints, although bone marrow and some osteocytes were positive (Figure 3).

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