The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats

ABSTRACT

Purpose: Aging is a known risk factor for osteoarthritis (OA). Several transgenic rodent models have been used to investigate the effects of accelerated or delayed aging in articular joints. However, age-effects on the progression of post-traumatic OA are less frequently evaluated. The objective of this study is to evaluate how animal age affects the severity of intra-articular inflammation and joint damage in the rat medial collateral ligament plus medial meniscus transection (MCLT+MMT) model of knee OA.

Methods: Forty-eight, male Lewis rats were aged to 3, 6, or 9 months old. At each age, eight rats received either an MCLT+MMT surgery or a skin-incision. At 2 months post-surgery, intra-articular evidence of CTXII, IL1β, IL6, TNFα, and IFNγ was evaluated using a multiplex magnetic capture technique, and histological evidence of OA was assessed via a quantitative histological scoring technique.

Results: Elevated levels of CTXII and IL6 were found in MCLT+MMT knees relative to skin-incision and contralateral controls; however, animal age did not affect the severity of joint inflammation. Conversely, histological investigation of cartilage damage showed larger cartilage lesion areas, greater width of affected cartilage, and more evidence of hypertrophic cartilage damage in MCLT+MMT knees with age.

Conclusions: These data indicate the severity of cartilage damage subsequent to MCLT+MMT surgery is related to the rat’s age at the time of injury. However, despite greater levels of cartilage damage, the level of intra-articular inflammation was not necessarily affected in 3, 6, and 9 month old male rats.

KEYWORDS:

• Knee osteoarthritis
• age
• meniscus injury
• intra-articular inflammation
• quantitative histology
• cartilage lesion morphometry

Acknowledgments

This work was supported by the National Institutes of Health under grants R01AR068424 and R01AR071335, and by graduate student fellowships from the Herbert Wertheim College of Engineering and J. Crayton Pruitt Family Department of Biomedical Engineering at the University of Florida. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the University of Florida.

Author Contributions

KDA devised the study, performed the animal surgeries, analyzed the data, authored the updated version of the GEKO software associated with the histological analyses and lesion morphometry measurements, and drafted the manuscript with the assistance of EGY and KMC. KMC managed the day-to-day care of the animals, organized the histological and magnetic capture samples, dissected the knees and processed these samples for histology, analyzed the histological data with KDA, and assisted in the creation of figures for the manuscript. EGY designed and conducted the multiplex magnetic capture assay, validated the assay, collected the magnetic capture data from the animals, and assisted with the drafting of magnetic capture methods. YYS graded histological slides and developed the capture-release proof of concept for TNFα. BDP graded histological slides and developed the capture-release proof of concept for IL1β. All authors have read and agree to the contents of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR068424,R01AR071335].