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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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Sulf-1 and Sulf-2 expression in murine temporomandibular joints. Safranin O staining (a-c) and immunohistochemistry (d-i) were performed on sections from temporomandibular joints of C57BL/6J mice at 6, 9, and 12 months of age (n = 6). Magnification: ×40.
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Figure 6: Sulf-1 and Sulf-2 expression in murine temporomandibular joints. Safranin O staining (a-c) and immunohistochemistry (d-i) were performed on sections from temporomandibular joints of C57BL/6J mice at 6, 9, and 12 months of age (n = 6). Magnification: ×40.

Mentions: TM joints from normal C57BL/6J mice (n = 6) were analyzed with safranin O staining (Figure 6a–c) and immunohistochemistry for Sulf-1 and Sulf-2 (Figure 6d–i). Histology showed thinning and reduced cell density in articular cartilage with increasing age (Figure 6c). In 6-month-old mice, only a few cells were positive for Sulf-1 but Sulf-2-positive cells were present throughout the cartilage. There was a marked increase in Sulf-2 expression at 9 months and in Sulf-1 expression at 12 months. In murine knee joints (n = 8), there was high Sulf expression at 1 month of age, followed by a decrease with joint maturation. Increased expression of Sulf-1 and Sulf-2 was seen in the articular cartilage of murine knee joints by 12 months of age, when early OA-like changes become apparent (Figure 7).


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)

Sulf-1 and Sulf-2 expression in murine temporomandibular joints. Safranin O staining (a-c) and immunohistochemistry (d-i) were performed on sections from temporomandibular joints of C57BL/6J mice at 6, 9, and 12 months of age (n = 6). Magnification: ×40.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Sulf-1 and Sulf-2 expression in murine temporomandibular joints. Safranin O staining (a-c) and immunohistochemistry (d-i) were performed on sections from temporomandibular joints of C57BL/6J mice at 6, 9, and 12 months of age (n = 6). Magnification: ×40.
Mentions: TM joints from normal C57BL/6J mice (n = 6) were analyzed with safranin O staining (Figure 6a–c) and immunohistochemistry for Sulf-1 and Sulf-2 (Figure 6d–i). Histology showed thinning and reduced cell density in articular cartilage with increasing age (Figure 6c). In 6-month-old mice, only a few cells were positive for Sulf-1 but Sulf-2-positive cells were present throughout the cartilage. There was a marked increase in Sulf-2 expression at 9 months and in Sulf-1 expression at 12 months. In murine knee joints (n = 8), there was high Sulf expression at 1 month of age, followed by a decrease with joint maturation. Increased expression of Sulf-1 and Sulf-2 was seen in the articular cartilage of murine knee joints by 12 months of age, when early OA-like changes become apparent (Figure 7).

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