Role of heparan sulfate 6-0 endosulfatases in intervertebral disc homeostasis

• Shuhei Otsuki ^[1] ; Oscar Alvarez-Garcia ^[2] ; Lotz, Martin K. ^[2] ; Masashi Neo ^[1]
  1. [1] Osaka Medical College

     Osaka Medical College

     Japón

     
  2. [2] Scripps Research Institute

     Scripps Research Institute

     Estados Unidos

     
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 34, Nº. 9, 2019, págs. 1051-1060
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • 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