Spondyloarthritis (SpA) is a chronic inflammatory joint disorder that initiates at
the enthesis, where tendons attach to bone through a fibrocartilage zone. At late
stages, excessive bone apposition appears within the diseased enthesis. Because Wnt5a
participates to normal bone formation and appears related to inflammatory processes,
we investigated the role of this Wnt growth factor in inflammation-associated ossification
in SpA. The concentration of Wnt5a assessed by enzyme-linked immunosorbent assay in
synovial fluids of patients with SpA (2.58 ± 0.98 ng/mL) was higher than in osteoarthritic
patients (1.33 ± 0.71 ng/mL). In murine primary cultures of tendon cells, chondrocytes,
and osteoblasts and in an organotypic model of mouse ankle, we showed that tumor necrosis
factor α reversibly diminished Wnt5a expression and secretion, respectively. Wnt5a
decreased gene expression of differentiation markers and mineralization in cultured
chondrocytes and reduced alkaline phosphatase activity in Achilles tendon enthesis
(−14%) and osteocalcin protein levels released by ankle explants (−36%). On the contrary,
Wnt5a stimulated ossification markers' expression in cultured osteoblasts and increased
the bone volume of the tibial plateau of the cultured explants (+19%). In conclusion,
our results suggest that Wnt5a is expressed locally in the joints of patients with
SpA. Wnt5a appears more associated with ossification than with inflammation and tends
to inhibit mineralization in chondrocytes and enthesis, whereas it seems to favor
the ossification process in osteoblasts and bone. Further studies are needed to decipher
the opposing effects observed locally in enthesis and systemically in bone in SpA.
Abbreviations:
ALP (alkaline phosphatase), ELISA (enzyme-linked immunosorbent assay), IL (interleukin), micro-CT (microcomputed tomography), MSC (mesenchymal stem cell), OA (osteoarthritis), RA (rheumatoid arthritis), SpA (spondyloarthritis), TNF (tumor necrosis factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 21, 2015
Accepted:
June 16,
2015
Received in revised form:
June 7,
2015
Received:
February 26,
2015
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
