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

Osteoarthritis Cartilage. 2019 Jan;27(1):118-128. doi: 10.1016/j.joca.2018.09.007. Epub 2018 Sep 22.


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.

Keywords: C-reactive protein; High-fat diet; Inflammation; Metabolic dysfunction; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / etiology*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • C-Reactive Protein / physiology*
  • Diet, High-Fat / adverse effects*
  • Humans
  • Lipid Metabolism / physiology
  • Macrophages / immunology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Monocytes / immunology
  • Osteoarthritis / etiology*
  • Osteoarthritis / immunology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteophyte / etiology
  • Osteophyte / physiopathology
  • Severity of Illness Index


  • C-Reactive Protein