Age-related effects on markers of inflammation and cartilage metabolism in response to an intra-articular lipopolysaccharide challenge in horses

Abstract

Eighteen Quarter Horses were used in a randomized complete design for a 28-d experiment to evaluate age-related effects on inflammation and cartilage turnover after induction of a single inflammatory insult using lipopolysaccharide (LPS). Horses were grouped by age as yearlings (3 males and 3 females), 2 to 3 yr olds (2/3 yr old; 2 males and 4 females), and skeletally mature 5 to 8 yr olds (mature; 2 males and 4 females). On d 0, all horses were individually housed and fed diets that met or exceeded requirements. On d 14, horses were challenged with an intra-articular injection of LPS. Radial carpal joints were randomly assigned to receive 0.5 ng LPS solution obtained from O55:B5 or 0.8 mL sterile lactated Ringer's solution as a contralateral control. Synovial fluid was collected prior to LPS injection at h 0 before injection and at 6, 12, 24, 168, and 336 h after injection. Samples were analyzed using commercial ELISA kits for PGE, collagenase cleavage neoepitope (C2C), and carboxypropeptide of type II collagen (CPII). Heart rate (HR), respiratory rate (RR), and rectal temperature (RT) were monitored over the initial 24 h and carpal circumference and surface temperature were also recorded, with additional measurements at 168 and 336 h. Data were analyzed using PROC MIXED of SAS. Values for RT, HR, and RR were within the normal range for each age group. Heart rate and RT were influenced by age ( < 0.01), whereas RR was unaffected ( ≤ 0.21). Joint circumference was not influenced by age of horse ( = 0.84), but circumference and surface temperature increased ( < 0.01) over time across all age groups. Synovial PGE concentrations tended ( = 0.09) to be influenced by age, with yearlings having lower ( = 0.03) concentrations than mature horses. Concentrations of synovial C2C were affected by age of horse, with yearlings and 2/3 yr olds having lower ( < 0.01) concentrations than mature horses. Similarly, synovial CPII was influenced by age, with yearlings and 2/3 yr olds having lower ( ≤ 0.02) concentrations than mature horses. Ratios of anabolic CPII to catabolic C2C varied by age, with mature and 2/3-yr-old horses having greater ( < 0.01) values compared with yearlings. These results indicate that inflammation and the corresponding cartilage turnover in response to LPS administration vary with age.

Evaluation of conjugated linoleic acid supplementation on markers of joint inflammation and cartilage metabolism in young horses challenged with lipopolysaccharide

“…Horses assigned to the control dietary treatment in the current study were used in conjunction with a previous study investigating the age-related effects on joint inflammation and cartilage metabolism (Kahn et al, 2017). Seventeen Quarter Horse yearlings (initial BW 354.0 ± 16.0 kg; 470 ± 26 d of age; 8 geldings and 9 fillies) were used in a randomized complete block design for a 56-d trial.…”

>b<Avaliação do queratam sulfato e ácido hialurônico presentes no líquido sinovial como biomarcadores das principais enfermidades articulares em equinos>/b<

“…Ainda, um estudo in vivo realizado em cavalos de corrida com lesões cárpicas identificou maiores concentrações de IL-6 associadas a presença de fragmentação osteocondral (LEY et al, 2007). Recentemente um estudo in vitro observou que o aumento na concentração de IL-6 ocorreu três dias após estimulo com IL-1β (SVALA et al, 2015), endossando estudos anteriores que relataram aumento na expressão gênica de IL-6 por condrócitos estimulados com IL-1β (DAVID et al, 2007 BACCARIN et al, 2014;KAHN et al, 2017). Aumento nas concentrações de PGE2…”

“…do LS tem sido demonstrado em vários modelos experimentais em resposta ao exercício (BACCARIN et al, 2014), à repetição da artrocentese em até 48 horas (FRISBIE et al, 2008;MOREIRA et al, 2015), à fragmentação osteocondral (FRISBIE et al, 2008;LAMPRECHT; WILLIAMS, 2012; MCILWRAITH; FRISBIE; KAWCAK, 2012b) e ao desafio com LPS (KAHN et al, 2017;LUCIA et al, 2013;NEUENSCHWANDER, 2016). Segundo Cunha et al (2017), nas doenças articulares de caráter inflamatório a produção de PGE2 pelos condrócitos é estimulada pela IL-1β.…”

“…Neste caso, a agressão ocorre diretamente na estrutura do colágeno por ação da catepsina K(DEJICA et al, 2012;MORT et al, 2016;NEUNDORF et al, 2010), levando a perda secundaria progressiva de proteoglicanos da MEC. Além disso, a lesão física celular estimula a degradação enzimática de proteoglicanos e colágeno, assim como a diminuição da síntese de componentes da MEC(FUNATO et al, 2017;LUCIA et al, 2013;MCILWRAITH, 2005;KAHN et al, 2017).Sinovite e capsulite consistem os problemas mais comuns nas articulações com OA e contribuem para o processo de degradação cartilagínea pela liberação de enzimas, mediadores inflamatórios e citocinas(BOYCE et al, 2013;TE MOLLER;VAN WEEREN, 2017;WANG et al, 2017). A importância da inflamação da membrana sinovial na patogênese da OA equina foi reportada por estudos experimentais(ANDREASSEN et al, 2017;BARRACHINA et al, 2016;VAN SICKLE, 1981; NEUENSCHWANDER, 2016) que a demonstraram que a degradação da cartilagem pode ocorrer na ausência de instabilidade ou traumas teciduais, e que a perda de GAGs está associada à ruptura inicial da superfície cartilagínea e à degradação da MEC.…”

“…Pinilla et al (2017) afirmam que há uma correlação positiva entre idade e as alterações histopatológicas cartilagíneas, endossando a hipótese de que animais mais velhos tendem a apresentar lesões mais graves(NEUNDORF et al, 2010) e maior resposta inflamatória(KAHN et al, 2017). Corroborando com a literatura, em nosso estudo observamos que os animais mais velhos, com idade entre sete e nove anos, eram portadores de OA, enfermidade com maior grau…”