Elsevier

Experimental Gerontology

Volume 55, July 2014, Pages 44-48
Experimental Gerontology

Short report
Influence of age on osteoarthritis progression after anterior cruciate ligament transection in rats

https://doi.org/10.1016/j.exger.2014.03.010Get rights and content

Highlights

  • The ACLT model of OA is widely used in young rats.

  • The development of OA after ACLT is significantly higher in middle-aged rats.

  • Age is a key factor in the ACLT model.

Abstract

The anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in young rats is widely used to study the pathogenesis of OA and possible treatment approaches. As aging is a key factor in the progression of this condition, it is hypothesized that animals may vary in their responses to ACLT according to their age. The histopathological features of young (2 month-old) and middle-aged (12 month-old) rats in the presence or absence of ACLT were compared. The results indicated that moderate degradative changes can be detected in the knee joints of sham-operated middle-aged rats compared with young animals. After ACLT, cartilage degradation was significantly higher in middle-aged rats in relation to young animals. An increase in interleukin(IL)-1β and IL-17 suggests the presence of a local inflammatory response represented by synovitis in ACLT rats which is not dependent on age. Our study indicates that age is an important factor affecting the pathogenesis of OA changes after ACLT and it should be considered in studies using this experimental model.

Introduction

Musculoskeletal conditions are a major cause of years lived with disability. Osteoarthritis (OA), the most common chronic joint condition, is characterized by focal loss of articular cartilage within synovial joints accompanied by bone alterations and different degrees of synovial inflammation (Woolf and Pfleger, 2003). Age is the strongest predictor of the development and progression of radiographic OA. Changes in the metabolism of articular cells with age affect joint properties (Gossan et al., 2013, Poulet et al., 2012) and likely OA treatment effectiveness (Ucar et al., 2013). Genetics, injuries and the overuse of joints can be factors contributing to OA development.

In addition to other mechanisms contributing to disease progression, by-products of matrix destruction and abnormal levels of cytokines and growth factors dysregulate the balance between anabolic and catabolic activities resulting in cartilage degradation (Aigner et al., 2007). Several lines of evidence indicate that inflammation plays a role in the progression of OA lesions (Fernandes et al., 2003). Pro-inflammatory cytokines such as interleukin(IL)-1β and IL-17 can synergise to damage the collagen fibril network leading to degradation products that can induce further degradation and chondrocyte death (Honorati et al., 2002, Koshy et al., 2002, Poole et al., 2003).

Injury to the anterior cruciate ligament (ACL) is a risk factor for knee OA (Amin et al., 2008, Lohmander et al., 2007, von Porat et al., 2004). The anterior cruciate ligament transection (ACLT) model induces joint changes analogous to those observed in post-traumatic human OA (Setton et al., 1999). The rat ACLT model can assist in understanding specific events such as progressive articular cartilage degradation, synovitis, subchondral bone sclerosis, and osteophyte formation during OA development (Hayami et al., 2006). In addition, it is widely used to evaluate new treatment approaches for OA. This model of joint instability is usually performed in young animals (around 2 month-old). Nevertheless, joint changes induced by surgery in skeletally immature rats may not mimic the development of OA in humans (Gerwin et al., 2010). In fact, middle-aged animals would be closer to the age range of patients with knee OA after injury to ACL (von Porat et al., 2004). Little is known about the influence of age on the rat ACLT model of OA. In this study, an ACLT in middle-aged and young rats was performed to investigate age-related changes in the response of knee joint tissues.

Section snippets

Animals

Young (age: 2 months; weight 313–366 g) and middle-aged (age 12 months; weight 480–550 g) male Wistar rats were obtained from Janvier (Le Genest Saint Isle, France). The animals were maintained at the animal house of the school of Pharmacy, University of Valencia, Spain. Water and food were provided ad libitum. All studies were performed in accordance with the European Union regulations for the handling and use of laboratory animals. The protocols were approved by the Institutional Animal Care and

Histopathological features

The score values for cartilage degradation, proteoglycan depletion and synovitis are shown in Fig. 1a. To clarify the expression of type II collagen in cartilage, the immunohistochemical analysis was performed in the patella, femora and tibia (Figs. 1b and 2). The two-way ANOVA revealed a significant age by ACLT interaction for cartilage degradation (F = 5.821; P = 0.0328). The cartilage degradation score in the presence of ACLT was significantly higher in middle-aged rats in relation to young

Conclusion

In conclusion, degenerative changes in articular tissues can be observed in sham-operated middle-aged rats with a significant reduction in type II collagen expression in comparison with young rats. We also show that ACLT induces a local inflammatory response mediated by cytokines such as IL-17 and IL-1β which is not affected by age. ACLT results in an enhanced cartilage degradation in 12 month-old rats compared with 2 month-old rats which indicates a higher response to the surgical induction of

Conflict of interest

The authors indicate no potential conflicts of interests.

Acknowledgments

This work was funded by grants from Bioibérica S.A. (Barcelona, Spain) (182/2010), Ministerio de Economía y Competitividad, ISCIII, FEDER (RETICEF RD12/0043/0013 and SAF2010-22048) and Generalitat Valenciana (Prometeo2010-047). The funding sources had no role in the design and conduct of the study; nor in the collection, management, analysis, data interpretation or the preparation of the manuscript. The authors thank Anna Blanco for her technical assistance.

References (20)

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