Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet

Kozijn, A.E.; Tartjiono, M.T.; Ravipati, S.; van der Ham, F.; Barrett, D.A.; Mastbergen, S.C.; Korthagen, N.M.; Lafeber, F.P.J.G.; Zuurmond, A.M.; Bobeldijk, I.; Weinans, H.; Stoop, R.

Abstract

Objective: C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of ‘metabolic’ OA.
Design: Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n = 30) and wild-type littermates (n = 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets.
Results: Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups.
Conclusions: Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development.

Citation

Kozijn, A., Tartjiono, M., Ravipati, S., van der Ham, F., Barrett, D., Mastbergen, S., …Stoop, R. (2019). Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet. Osteoarthritis and Cartilage, 27(1), 118-128. https://doi.org/10.1016/j.joca.2018.09.007

• Journal Article Type: Article
• Acceptance Date: Sep 13, 2018
• Online Publication Date: Sep 22, 2018
• Publication Date: Jan 1, 2019
• Deposit Date: Dec 18, 2018
• Publicly Available Date: Dec 19, 2018
• Journal: Osteoarthritis and Cartilage
• Print ISSN: 1063-4584
• Electronic ISSN: 1522-9653
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 1
• Pages: 118-128
• DOI: https://doi.org/10.1016/j.joca.2018.09.007
• Keywords: Rheumatology; Orthopedics and Sports Medicine; Biomedical Engineering
• Public URL: https://nottingham-repository.worktribe.com/output/1423257
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1063458418314730?via%3Dihub