Fib3-3 as a biomarker for osteoarthritis in a rat model with metabolic dysregulation

Fib3-3 as a biomarker for osteoarthritis in a rat model with metabolic dysregulation

de Visser, Huub M. (University Medical Center Utrecht)
Sanchez, Christelle (Universite de Liege)
Mastbergen, Simon C. (University Medical Center Utrecht)
Lafeber, Floris P.J.G. (University Medical Center Utrecht)
Henrotin, Yves E. (Universite de Liege)
Weinans, H.H. (TU Delft Biomaterials & Tissue Biomechanics; University Medical Center Utrecht)

2019

Objective: Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage. Design: Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3. Results: Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration (r = 0.435) and cartilage degeneration (r = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage. Conclusions: In the rat groove model combined with high-fat diet–induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis.

animal model
articular cartilage
osteoarthritis; biomarker

http://resolver.tudelft.nl/uuid:e0a899ca-ec0d-43d5-a555-6ae61fe8cc38

https://doi.org/10.1177/1947603518754629

1947-6035

Cartilage, 10 (3), 329-334

Institutional Repository

journal article

© 2019 Huub M. de Visser, Christelle Sanchez, Simon C. Mastbergen, Floris P.J.G. Lafeber, Yves E. Henrotin, H.H. Weinans