title: Wnt5a is expressed in spondyloarthritis and exerts opposite effects on enthesis and bone in murine organ and cell cultures.
abstract: 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.
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université Claude Bernard-Lyon 1, Université de Lyon, UMR CNRS 5246, Villeurbanne, France. Electronic address: carole.bougault@univ-lyon1.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Bougault
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université Claude Bernard-Lyon 1, Université de Lyon, UMR CNRS 5246, Villeurbanne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Briolay
authors.affiliation: Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, INSERM, UMR957, Nantes, France.
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Boutet
authors.affiliation: Laboratoire d'ingénierie ostéoarticulaire et dentaire, INSERM, UMRS 791, Nantes, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.affiliation: Physiopathology of Inflammatory Bone Diseases, Université du Littoral-Côte d'Opale, EA 4490, Boulogne-sur-Mer, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Delplace
authors.affiliation: Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, INSERM, UMR957, Nantes, France; Department of Rheumatology, Hôtel-Dieu, CHU de Nantes, Nantes, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Le Goff
authors.affiliation: Laboratoire d'ingénierie ostéoarticulaire et dentaire, INSERM, UMRS 791, Nantes, France; UFR Odontologie, Université de Nantes, Nantes, France; PHU4 OTONN, CHU de Nantes, Nantes, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guicheux
authors.affiliation: Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, INSERM, UMR957, Nantes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université Claude Bernard-Lyon 1, Université de Lyon, UMR CNRS 5246, Villeurbanne, France.
authors.forename: David
authors.initials: D
authors.lastname: Magne
mesh_terms: D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D001842:Bone and Bones / Q000503:physiopathology*; D002478:Cells, Cultured; D007592:Joint Diseases / Q000378:metabolism*; D051379:Mice; D009924:Organ Culture Techniques; D013582:Synovial Fluid / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse