The repair of full-thickness articular cartilage defect using intra-articular administration of N-acetyl-D-glucosamine in the rabbit knee: randomized controlled trial.

Nai-Jen Chang,Hsueh-Chun Wang,Horng-Chaung Hsu,Chih-Chan Lin,Ming-Long Yeh,Yi-Ting Lin

doi:10.1186/s12938-015-0100-y

Abstract

BackgroundAlthough various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached. Glucosamine (GlcN) is widely used as a nutritional supplement. However, the clinical- evidence-based outcome of GlcN administration remains controversial. N-acetyl-d-glucosamine (GlcNAc), a derivative of GlcN, shows chondroprotective activity and mediates the activation of articular chondrocytes. Therefore, we investigated the effect of intra-articular administration of GlcNAc in rabbits’ knee joints with experimental full-thickness articular cartilage (FTAC) defects.MethodsTwelve male adult New Zealand white rabbits, providing 24 knees, were used in this study. FTAC defects were created in the high-weight-bearing area of the medial femoral condyles of bilateral knees. All rabbits were randomly allocated to analysis at postsurgical week 4 or postsurgical week 12. In the week 4 group, rabbits’ knees (six per group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 3 weeks, beginning 1 week postoperatively. In the week 12 group, the rabbits’ knees (six in each group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 4 weeks, beginning 1 week postoperatively. Rabbits were sacrificed at 4 or 12 weeks after surgery for macroscopic, histological and radiological examinations of the knee joints.ResultsAll rabbits had no systemic or local adverse effects. The saline and GlcNAc groups showed visible differences in healing of the FTAC defect at the end of testing. At week 4, the GlcNAc group had a higher level of collagen type II (COL II) and showed up-regulated production of transforming growth factor (TGF)-β2 and TGF-β3, suggesting the involvement of endogenous growth factors. At week 12, the GlcNAc group displayed formation of hyaline-like cartilage regeneration with mature chondrocytes (SOX9+), robust glycosaminoglycan (GAG) content, and positive COL II content in both the adjacent cartilage and reparative sites. However, the saline group demonstrated mainly fibrocartilage scar tissue, indicating COL I expression. Furthermore, the GlcNAc group had significantly higher bone volume per tissue volume and higher trabecular thickness than the saline group.ConclusionsIntra-articular GlcNAc may promote the repair of experimental FTAC defects in the rabbit knee joint model.

Highlights

Various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached
Current clinical therapeutic treatments for cartilage repair include intra-articular therapy, e.g., non-steroidal anti-inflammatory drugs, corticosteroids, dextrose prolotherapy, hyaluronic acid (HA) or platelet-rich plasma [1, 2], microfracture, autologous chondrocyte implantation, and osteochondral transplantation techniques [3, 4]. These treatment options, for large cartilage defects, present the formation of fibrocartilage scar tissue and poor integration of hyaline cartilage in the host [5, 6]. Regarding their effectiveness for large cartilage lesions, there is a lack of both clinical consensus and reproducible evidence that currently available treatment significantly changes the progression of osteoarthritis, based on prospective, randomized studies [7,8,9]
At week 4, the defect areas in both the saline and GlcNAc groups were visibly concave new tissue had developed inwards from the outer area of the defect edges

Summary

Introduction

Various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached. Current clinical therapeutic treatments for cartilage repair include intra-articular therapy, e.g., non-steroidal anti-inflammatory drugs, corticosteroids, dextrose prolotherapy, hyaluronic acid (HA) or platelet-rich plasma [1, 2], microfracture, autologous chondrocyte implantation, and osteochondral transplantation techniques [3, 4]. These treatment options, for large cartilage defects, present the formation of fibrocartilage scar tissue and poor integration of hyaline cartilage in the host [5, 6]. GlcNAc, classified as a monosaccharide derived from glucose, has a relatively stable structure

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