Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model

• Published in: Scientific reports Vol. 8; no. 1; pp. 3492 - 10
• Main Authors: Courbon, Guillaume, Lamarque, Raphaëlle, Gerbaix, Maude, Caire, Robin, Linossier, Marie-Thérèse, Laroche, Norbert, Thomas, Mireille, Thomas, Thierry, Vico, Laurence, Marotte, Hubert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.02.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 631/250/249/1313/498; 631/250/808; 631/80/304; Animal models; Animals; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - physiopathology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - physiopathology; Bone growth; Bone histomorphometry; Bone imaging; Bone loss; Bone Morphogenetic Proteins - genetics; Cancellous bone; Cortical bone; Cytokines; Disease Models, Animal; Dkk1 protein; Female; Frizzled protein; Frizzled-related protein 1; Gene Expression Regulation, Developmental - genetics; Genetic Markers - genetics; Humanities and Social Sciences; Humans; Inflammation; Intercellular Signaling Peptides and Proteins - genetics; Kinetics; Membrane Proteins - genetics; multidisciplinary; Osteoclasts; Osteoclasts - metabolism; Osteocytes - metabolism; Osteogenesis; Osteogenesis - genetics; Porosity; RANK Ligand - genetics; Rats; Rheumatoid arthritis; Science; Science (multidisciplinary); SOST protein; TRANCE protein; Wnt protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-21886-w

Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.