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AB0050 Impaired adiponectin and leptin levels during osteoarthritis onset and development in str/ort mice
  1. R Giambelli,
  2. SK Bernini,
  3. M Perrella,
  4. A Grotti,
  5. R Cavagnoli,
  6. G Samuelli,
  7. P Garofalo,
  8. T Zanelli,
  9. G Caselli,
  10. LC Rovati
  1. Rottapharm Biotech, Monza, Italy

Abstract

Background Obesity is a risk factor for osteoarthritis (OA). In obese subjects OA develops not only in weight-bearing joints but also in non-weight-bearing joints, suggesting that dysregulated metabolism in obese patients may promote OA onset.

As obesity evolves many physiological parameters are dysregulated, including the levels of adipokine hormones such as leptin and adiponectin. For this reason, it has been suggested that adipokine levels in serum and synovial fluid are associated with a worsening of synovial inflammation and OA progression in these patients(1).

In vivo and in vitro studies show that high levels of leptin induce the synthesis of metalloproteases involved in cartilage degradation(2). Conversely, dietary-induced weight loss is associated with increased adiponectin serum levels and reduced loss of tibial and femoral cartilage volume, suggesting a protective role of adiponectin in OA.

STR/ort mice are an animal model of spontaneous OA characterized by early pathology development (at about 20 weeks) and dysregulated metabolism(3). Notably, these mice have adiponectin serum levels lower than those found in control mouse strains(4).

Objectives To evaluate whether adiponectin and leptin serum levels are associated with OA development and/or progression in STR/ort mice.

Methods First, we measured the time course of adipokine levels in STR/ort mice before the onset of OA (at 8, 14 and 20 weeks of age), and in age-matched CBA control mice. Then, we calculated the ratio leptin/adiponectin (L/A) in the serum of STR/ort mice during OA progression (at 20, 30 and 40 weeks). Blood samples were collected from caudal vein (time course) or from vena cava at sacrifice, when knee joints were collected, processed for histology and blindly scored according to OARSI and Mankin's methods.

Results Adiponectin serum levels in STR/ort mice at 8, 14 and 20 weeks were significantly lower than in age-matched CBA mice. Instead, leptin serum levels in STR/ort mice were higher than in CBA strain at 14 and 20 weeks. Consequently, there was a relevant difference in the ratio L/A between the two strains, with greater L/A values in STR/ort mice at 14 and 20 weeks. (Table 1)

In STR/ort mice, the ratio L/A tended to further increase between 30 and 20 weeks (1.73±0.16 from 1.28±0.17, respectively), in parallel with the increase in OARSI scores of knee joints (11.1±1.5 vs 8.4±1.3). The histopathological score increased in STR/ort mice even between 30 and 40 weeks, but without a concomitant increase in the ratio L/A.

Conclusions We show for the first time that leptin serum levels and the ratio L/A in STR/ort mice are higher than in CBA mice, and that the ratio L/A in STR/ort mice increases as their histopathological scores worsen. We suggest that dysregulated levels of these adipokines may be associated or even precede OA development in this animal model.

References

  1. King L.K. et al. Osteoarthritis and Cartilage, 2015.

  2. Bao J.P. et all. Mol Biol Rep. 2010.

  3. Uchida K. et al. Experimental Animals, 2009.

  4. Giambelli R. et al. Osteoarthtis and Cartilage Volume 24, Supplement 1, April 2016, Pages S85.

References

Disclosure of Interest None declared

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