Affordable Access

Access to the full text

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

Authors
  • Briolay, Anne1
  • El Jamal, Alaeddine1
  • Arnolfo, Paul2, 3
  • Le Goff, Benoît2, 3
  • Blanchard, Frédéric2
  • Magne, David1
  • Bougault, Carole1
  • 1 Univ Lyon, Univ Claude Bernard Lyon 1, CNRS UMR 5246, ICBMS, Lyon, F-69622, France , Lyon (France)
  • 2 Nantes University, Nantes, France , Nantes (France)
  • 3 CHU Nantes, Nantes, France , Nantes (France)
Type
Published Article
Journal
Arthritis Research & Therapy
Publisher
Springer Science and Business Media LLC
Publication Date
Oct 12, 2020
Volume
22
Issue
1
Identifiers
DOI: 10.1186/s13075-020-02330-9
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundExcessive bone formation in the entheses is one of the features of peripheral spondyloarthritis (SpA). Complex pathological mechanisms connecting inflammation, mechanical stress, and ossification are probably involved. We focused on bone morphogenetic protein (BMP)-2, -4, and -7 as possible mediators of this process.MethodsBMP-2, -4, and -7 concentration was measured by ELISA in synovial fluids (SFs) of SpA (n = 56) and osteoarthritic (n = 21) patients. Mouse organotypic ankle cultures were challenged by a pro-inflammatory cocktail. Mouse primary chondrocytes, osteoblasts, or tenocytes were treated with TNF-α, interleukin (IL)-17, or IL-22 and/or subjected to cyclic stretch, or with recombinant BMP-2 or -4.ResultsIn SpA SFs, if BMP-7 was barely detectable, BMP-2 concentration was higher and BMP-4 was lower than in osteoarthritic samples, so that BMP-2/BMP-4 ratio augmented 6.5 folds (p < 0.001). In SpA patients, TNF-α, IL-6, and IL-17 levels correlated this ratio (n = 21). Bmp-2/Bmp-4 ratio was similarly enhanced by cytokine treatment in explant and cell cultures, at mRNA level. In particular, simultaneous application of TNF-α and cyclical stretch induced a 30-fold increase of the Bmp-2/Bmp-4 ratio in chondrocytes (p = 0.027). Blockade of prostaglandin E2 and IL-6 production had almost no effect on the stretch-induced regulation of Bmp-2 or -4. Osteoinductive effects of BMP-4, and to a lesser extend BMP-2, were identified on cultured chondrocytes and tenocytes.ConclusionsOur results first settle that BMP factors are locally deregulated in the SpA joint. An unexpected decrease in BMP-4 could be associated to an increase in BMP-2, possibly in response to mechanical and/or cytokine stimulations.

Report this publication

Statistics

Seen <100 times