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

Autor: Thierry Thomas, Mireille Thomas, Laurence Vico, Robin Caire, Marie-Thérèse Linossier, Guillaume Courbon, Raphaëlle Lamarque, Norbert Laroche, Maude Gerbaix, Hubert Marotte
Rok vydání: 2017
Předmět:
0301 basic medicine
musculoskeletal diseases
Genetic Markers
medicine.medical_specialty
Science
Arthritis
Osteoclasts
Inflammation
Osteocytes
Article
Proinflammatory cytokine
Arthritis
Rheumatoid
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Osteogenesis
Internal medicine
medicine
Animals
Humans
030203 arthritis & rheumatology
Multidisciplinary
biology
business.industry
RANK Ligand
Gene Expression Regulation
Developmental
Membrane Proteins
medicine.disease
Arthritis
Experimental
Bone Formation Inhibition
Rats
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Endocrinology
chemistry
RANKL
Osteocyte
Rheumatoid arthritis
Bone Morphogenetic Proteins
biology.protein
Medicine
Sclerostin
Intercellular Signaling Peptides and Proteins
Female
medicine.symptom
business
Zdroj: Scientific Reports
Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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