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Expression of novel extracellular sulfatases Sulf-1 and Sulf-2 in normal and osteoarthritic articular cartilage.

Otsuki S, Taniguchi N, Grogan SP, D'Lima D, Kinoshita M, Lotz M - Arthritis Res. Ther. (2008)

Bottom Line: OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage.The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage.This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. otsuki@scripps.edu

ABSTRACT

Introduction: Changes in sulfation of cartilage glycosaminoglycans as mediated by sulfatases can regulate growth factor signaling. The aim of this study was to analyze expression patterns of recently identified extracellular sulfatases Sulf-1 and Sulf-2 in articular cartilage and chondrocytes.

Methods: Sulf-1 and Sulf-2 expressions in human articular cartilage from normal donors and patients with osteoarthritis (OA) and in normal and aged mouse joints were analyzed by real-time polymerase chain reaction, immunohistochemistry, and Western blotting.

Results: In normal articular cartilage, Sulf-1 and Sulf-2 mRNAs and proteins were expressed predominantly in the superficial zone. OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage. Sulf protein expression in OA cartilage was prominent in the cell clusters. Western blotting revealed a profound increase in Sulf protein levels in human OA cartilage. In normal mouse joints, Sulf expression was similar to human cartilage, and with increasing age, there was a marked upregulation of Sulf.

Conclusion: The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage. Sulf mRNA and protein levels are increased in aging and OA cartilage. This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA.

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Localization of Sulf-1 and Sulf-2 in normal cartilage. Representative sections of 26-year-old (a, d) and 74-year-old (g) normal cartilage (Mankin scores: 0 and 2) as seen on safranin O staining are shown (n = 8; 19 to 37 years old). Sulf-positive cells (brown staining) are present in the superficial zone and the top of the middle zone, and Sulf-2 expression is greater than Sulf-1 (b, c, e, f, h, i) in both young and old cartilage. Magnifications: ×10 (a-c) and ×40 (d-i).
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Figure 2: Localization of Sulf-1 and Sulf-2 in normal cartilage. Representative sections of 26-year-old (a, d) and 74-year-old (g) normal cartilage (Mankin scores: 0 and 2) as seen on safranin O staining are shown (n = 8; 19 to 37 years old). Sulf-positive cells (brown staining) are present in the superficial zone and the top of the middle zone, and Sulf-2 expression is greater than Sulf-1 (b, c, e, f, h, i) in both young and old cartilage. Magnifications: ×10 (a-c) and ×40 (d-i).

Mentions: Young and old normal samples as seen on safranin O staining (Figure 2a, d, g) had only a few Sulf-positive cells in the superficial zone (Figure 2b, c, e, f, h, i) and no positive cells in the middle and deep zones. In general, the expression of Sulf-2 appeared more intense than Sulf-1 in normal cartilage. In OA cartilage, many positive cells were detected, especially in chondrocyte clusters (Figure 3g, h, k, l). The representative example of 65-year-old cartilage had both normal areas (Mankin score: 2) (Figure 3a, b) and OA areas with fibrillations and cluster formation (Mankin score: 8) (Figure 3c, d). The normal appearing areas from OA joints had 18.5% Sulf-1-positive and 31.9% Sulf-2-positive cells in the superficial zone (Figure 3e, f, i, j), which was greater than in normal cartilage (Figure 2). On the other hand, OA areas had 75.3% Sulf-1-positive and 73.2% Sulf-2-positive cells (Figure 3g, h, k, l).


Expression of novel extracellular sulfatases Sulf-1 and Sulf-2 in normal and osteoarthritic articular cartilage.

Otsuki S, Taniguchi N, Grogan SP, D'Lima D, Kinoshita M, Lotz M - Arthritis Res. Ther. (2008)

Localization of Sulf-1 and Sulf-2 in normal cartilage. Representative sections of 26-year-old (a, d) and 74-year-old (g) normal cartilage (Mankin scores: 0 and 2) as seen on safranin O staining are shown (n = 8; 19 to 37 years old). Sulf-positive cells (brown staining) are present in the superficial zone and the top of the middle zone, and Sulf-2 expression is greater than Sulf-1 (b, c, e, f, h, i) in both young and old cartilage. Magnifications: ×10 (a-c) and ×40 (d-i).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483452&req=5

Figure 2: Localization of Sulf-1 and Sulf-2 in normal cartilage. Representative sections of 26-year-old (a, d) and 74-year-old (g) normal cartilage (Mankin scores: 0 and 2) as seen on safranin O staining are shown (n = 8; 19 to 37 years old). Sulf-positive cells (brown staining) are present in the superficial zone and the top of the middle zone, and Sulf-2 expression is greater than Sulf-1 (b, c, e, f, h, i) in both young and old cartilage. Magnifications: ×10 (a-c) and ×40 (d-i).
Mentions: Young and old normal samples as seen on safranin O staining (Figure 2a, d, g) had only a few Sulf-positive cells in the superficial zone (Figure 2b, c, e, f, h, i) and no positive cells in the middle and deep zones. In general, the expression of Sulf-2 appeared more intense than Sulf-1 in normal cartilage. In OA cartilage, many positive cells were detected, especially in chondrocyte clusters (Figure 3g, h, k, l). The representative example of 65-year-old cartilage had both normal areas (Mankin score: 2) (Figure 3a, b) and OA areas with fibrillations and cluster formation (Mankin score: 8) (Figure 3c, d). The normal appearing areas from OA joints had 18.5% Sulf-1-positive and 31.9% Sulf-2-positive cells in the superficial zone (Figure 3e, f, i, j), which was greater than in normal cartilage (Figure 2). On the other hand, OA areas had 75.3% Sulf-1-positive and 73.2% Sulf-2-positive cells (Figure 3g, h, k, l).

Bottom Line: OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage.The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage.This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. otsuki@scripps.edu

ABSTRACT

Introduction: Changes in sulfation of cartilage glycosaminoglycans as mediated by sulfatases can regulate growth factor signaling. The aim of this study was to analyze expression patterns of recently identified extracellular sulfatases Sulf-1 and Sulf-2 in articular cartilage and chondrocytes.

Methods: Sulf-1 and Sulf-2 expressions in human articular cartilage from normal donors and patients with osteoarthritis (OA) and in normal and aged mouse joints were analyzed by real-time polymerase chain reaction, immunohistochemistry, and Western blotting.

Results: In normal articular cartilage, Sulf-1 and Sulf-2 mRNAs and proteins were expressed predominantly in the superficial zone. OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage. Sulf protein expression in OA cartilage was prominent in the cell clusters. Western blotting revealed a profound increase in Sulf protein levels in human OA cartilage. In normal mouse joints, Sulf expression was similar to human cartilage, and with increasing age, there was a marked upregulation of Sulf.

Conclusion: The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage. Sulf mRNA and protein levels are increased in aging and OA cartilage. This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA.

Show MeSH
Related in: MedlinePlus