Autor: |
Otsuki S; Department of Orthopedic Surgery, Osaka Medical College, Japan. ort182@osaka-med.ac.jp., Alvarez-Garcia O; Department of Molecular Medicine, The Scripps Research Institute, USA., Lotz MK; Department of Molecular Medicine, The Scripps Research Institute, USA., Neo M; Department of Orthopedic Surgery, Osaka Medical College, Japan. |
Jazyk: |
angličtina |
Zdroj: |
Histology and histopathology [Histol Histopathol] 2019 Sep; Vol. 34 (9), pp. 1051-1060. Date of Electronic Publication: 2019 Mar 29. |
DOI: |
10.14670/HH-18-107 |
Abstrakt: |
The expression of heparan sulfate endosulfatases (Sulfs) was investigated in the intervertebral disc (IVD) to clarify their role in IVD homeostasis. Sulf-1 and -2 expression were elucidated in normal and degenerated human IVD. Age-related effects on Sulf expression, type II collagen levels, and structural changes were analyzed in IVDs of wild-type (WT) and Sulf-1 knockout (Sulf-1⁻/⁻) mice. The effect of recombinant Sulf-1 (100 ng/ml) and Sulf-1 knockdown on heparan sulfate proteoglycan and collagen expression in ATDC5 cells were examined. Finally, the effect of Sulf-1 on transforming growth factor (TGF) β1-induced signaling was evaluated. Results show that Sulf-1 and -2 levels were higher in degenerated human IVDs. In WT mice, Sulf-1 and -2 expression generally declined as the animals aged. In particular, Sulf-1 in the nucleus pulposus was higher compared with Sulf-2 at the age of 1 and 6 months and significantly declined with aging. Sulf-1⁻/⁻ mice showed more severe IVD pathology than WT mice, with lower type II collagen levels in nucleus pulposus, and degeneration with type I collagen in annulus fibrosus. In vitro, Sulf-1 induced type II collagen expression and significantly increased TGF-β1-induced Smad2/3 phosphorylation in ATDC5 cells. In conclusion, Sulf-1 might play a critical role from development to maintenance of IVD homeostasis by regulating collagen expression. |
Databáze: |
MEDLINE |
Externí odkaz: |
|