Intra-articular Injection of Hyaluronan Diminishes Loss of Chondrocytes in a Rat Immobilized-Knee Model

Abstract

Joint immobilization is a useful and common treatment modality in orthopedics. However, it also causes unfavorable outcome such as articular cartilage degeneration. Intra-articular injection of hyaluronan has been accepted as a treatment of osteoarthritis, but its effects on immobilized joint remain to be clarified. Hyaluronan is a polysaccharide, distributed ubiquitously in various tissues. In this study, we examined the effect of hyaluronan on the articular cartilage in immobilized joints. The unilateral knee joints of adult male rats were immobilized at 150° in flexion with an internal plate and screws for 1, 2, 4, 6, 8, 12, or 16 weeks (n = 84). Hyaluronan or saline (50 μ l/each injection) was administered intra-articularly on the day of surgery and once a week. The articular cartilage from the medial midcondylar region of the knee was obtained, and divided into non-contact, contact and transitional areas (between the non-contact and the contact areas). In each area, a degree of degeneration was evaluated by histomorphometric grading, and measurements of thickness and number of chondrocytes. Histological grading scores in the hyaluronan group were smaller at 12 and 16 weeks compared with those in the saline group. The thickness of the articular cartilage increased in the transitional area in both groups. The number of chondrocytes in the contact and transitional areas gradually decreased, but their number in the hyaluronan group was greater at 12 and 16 weeks compared with that in the saline group. Hyaluronan showed chondroprotective effects on the articular cartilage in a rat immobilized-knee model.

Reversibility of Immobilization-Induced Articular Cartilage Degeneration after Remobilization in Rat Knee Joints

“…Forty-eight adult male Sprague-Dawley rats aged 12 weeks were prepared for histology. Unilateral knee joints of the rats were rigidly immobilized at 150° of flexion with a plastic plate and metal screws as previously described (Hagiwara et al 2006;Ando et al 2008). Sham-operated rats had holes drilled in the femur and tibia with metal screws inserted, but without a plate.…”

“…The decalcified specimens were then embedded in paraffin. Five-μm serial sections were obtained at the medial midcondylar region in sagittal plane as previously described (Hagiwara et al 2006;Ando et al 2008).…”

“…Transitional area is the area between the contact and non-contact areas, and contacts to the anterior meniscus. Modified Mankin's histological grading scheme, thickness of the articular cartilage, and cell density in each area were blindly measured by a single observer as previously described (Ando et al 2008;Hagiwara et al 2009). Modified Mankin's histological grading scheme was used for evaluation of the articular cartilage degeneration (Sakakibara et al 1994;Ando et al 2008;Hagiwara et al 2009).…”

Resistance exercise recovers the structure of cartilage and synovial membrane of the ankle joint of rats after sciatic compression

“…In relation to the animals in the LEG group, in general terms, tissue reorganization of the articular cartilage and the synovial membrane were observed, indicating that the resistance exercise accelerated the recovery of the articular constituents. According to Ando, Hagiwara, Chimoto, Hatori, Onoda, Itoi 30 , the restoration of movement reduces articular stiffness and improves the flow of synovial fluid in the articular cavity, which promotes the nutrition of the cartilage and its consequent regeneration. Physical exercise has been seen as an important tool in maintaining the integrity of the cartilage, preventing degeneration and maintaining its biomechanical properties 49 .…”

“…Then the protocol for fixing in paraffin and microtome was performed, with 7 µm cuts using an Olympus ® CUT 4055 microtome. The slides of the sagittal section of the joint were stained with hematoxylin and eosin 29 for general morphology and with Fast Green 30 for the articular cartilage. The morphological and morphometric analyses of the articular tissues were performed using a light microscope (Olympus ® ) and the visual fields of interest were photomicrographed using 20 and 40 lenses.…”