Publication: Role of heparan sulfate 6-0 endosulfatases in intervertebral disc homeostasis
Authors
Otsuki, Shuhei ; Alvarez Garcia, Oscar ; Lotz, Martin K. ; Neo, Masashi
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
DOI: 10.14670/HH-18-107
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info:eu-repo/semantics/article
Description
Abstract
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.
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Citation
Histology and Histopathology, Vol.34, nº9, (2019)
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