Age-dependent differences in response to partial-thickness cartilage defects in a rat model as a measure to evaluate the efficacy of interventions for cartilage repair

Yorikazu Akatsu,Taisuke Fukawa,Yohei Yamamoto,Ryuichiro Akagi,Jun Endo,Takahisa Sasho,Takahiro Enomoto,Toshihide Sasaki,Hiroko Hoshi,Masamichi Tahara,Satoshi Yamaguchi,Kazuhisa Takahashi

doi:10.1007/s00441-018-2914-y

Abstract

The objectives of this study are (1) to examine age-dependent longitudinal differences in histological responses after creation of partial-thickness articular cartilage defects (PTCDs) in rats and to use this model (2) to objectively evaluate the effectiveness of interventions for cartilage repair. Linear PTCDs were created at a depth of 100 μm in the weight-bearing region of the medial femoral condyle in rats of different ages (3 weeks, 6 weeks, 10 weeks and 14 weeks). One day, one week, two weeks, four weeks and twelve weeks after PTCD generation, spontaneous healing was evaluated histologically and immunohistochemically. Effects of interventions comprising mesenchymal stem cells (MSCs) or platelet-rich plasma (PRP) or both on 14-week-old PTCD rats were evaluated and compared with natural courses in rats of other ages. Younger rats exhibited better cartilage repair. Cartilage in 3-week-old and 6-week-old rats exhibited nearly normal restoration after 4–12 weeks. Cartilage in 14-week-old rats deteriorated over time and early signs of cartilage degeneration were observed. With injection of MCSs alone or MSCs + PRP, 14-week-old PTCD rats showed almost the same reparative cartilage as 6-week-old rats. With injection of PRP, 14-week-old PTCD rats showed almost the same reparative cartilage as 10-week-old rats. This model will be of great use to objectively compare the effects of interventions for small cartilage lesions and may help to advance the development of disease-modifying osteoarthritis drugs.

Highlights

Osteoarthritis (OA) of the knee joint detrimentally affects the activities of daily living of the elderly and is costly to manage, resulting in a significant burden on social welfare programs, Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Cell Tissue Res (2019) 375:425–435(Lu et al 2006; Mankin 1974; Mizuta et al 2004)
We previously reported that partial-thickness articular cartilage defects (PTCDs) resolved naturally in 3-week-old Sprague Dawley (SD) rats but was incurable in 16-week-old rats (Tsuruoka et al 2011)
The parapatellar medial approach was used to open the knee joint and a linear PTCD was created in the weight-bearing region of the medial femoral condyle (MFC) in both knees in the direction of joint motion (Yoshioka et al 1998) by using a specially designed 100-μm scalpel modified from an ophthalmic knife

Summary

Introduction

PTCD is a minor defect compared with FTCD, it does not heal spontaneously and leads to the onset of OA. PTCD on the femoral side induces degeneration of the surrounding cartilage as well as degeneration on the tibial side, followed by progression to OA (Marijnissen et al 2002; Mastbergen et al 2006). An earlier study reported that PTCD is restorable during the embryonic stage in experimental animals and in very immature individuals (Namba et al 1998). Elucidation of the mechanism causing this difference may directly lead to the development of new therapies for PTCD. Previous studies failed to define the age at which PTCD is restorable in SD rats

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