PURPOSE: To determine the role of Indian hedgehog (Ihh) signaling in human cartilage endplate (CEP) degeneration. METHODS: CEP-degenerated tissues from patients with Modic I or II changes (n = 9 and 45, respectively) and normal tissues from vertebral burst fracture patients (n = 17) were collected. Specimens were either cut into slices for organ culture ex vivo or digested to isolate chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on cartilage degeneration were determined by investigating degeneration markers in this study. RESULTS: Ihh expression and cartilage degeneration markers significantly increased in the Modic I and II groups. The expression of cartilage degeneration markers was positively correlated with degeneration severity. Gain-of-function for Ihh promoted expression of cartilage degeneration markers in vitro, while loss-of-function for Ihh inhibited their expression both in vitro and ex vivo. CONCLUSIONS: These findings demonstrated that Ihh promotes CEP degeneration. Blocking Ihh pathway has potential clinical usage for attenuating CEP degeneration.
PURPOSE: To determine the role of Indian hedgehog (Ihh) signaling in humancartilage endplate (CEP) degeneration. METHODS: CEP-degenerated tissues from patients with Modic I or II changes (n = 9 and 45, respectively) and normal tissues from vertebral burst fracturepatients (n = 17) were collected. Specimens were either cut into slices for organ culture ex vivo or digested to isolate chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on cartilage degeneration were determined by investigating degeneration markers in this study. RESULTS:Ihh expression and cartilage degeneration markers significantly increased in the Modic I and II groups. The expression of cartilage degeneration markers was positively correlated with degeneration severity. Gain-of-function for Ihh promoted expression of cartilage degeneration markers in vitro, while loss-of-function for Ihh inhibited their expression both in vitro and ex vivo. CONCLUSIONS: These findings demonstrated that Ihh promotes CEP degeneration. Blocking Ihh pathway has potential clinical usage for attenuating CEP degeneration.
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Authors: Swenja Kröller-Schön; Andreas Daiber; Sebastian Steven; Matthias Oelze; Katie Frenis; Sanela Kalinovic; Axel Heimann; Frank P Schmidt; Antonio Pinto; Miroslava Kvandova; Ksenija Vujacic-Mirski; Konstantina Filippou; Markus Dudek; Markus Bosmann; Matthias Klein; Tobias Bopp; Omar Hahad; Philipp S Wild; Katrin Frauenknecht; Axel Methner; Erwin R Schmidt; Steffen Rapp; Hanke Mollnau; Thomas Münzel Journal: Eur Heart J Date: 2018-10-07 Impact factor: 29.983