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

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.

Molecular Validation of Chondrogenic Differentiation and Hypoxia Responsiveness of Platelet-Lysate Expanded Adipose Tissue–Derived Human Mesenchymal Stromal Cells

“…Previous studies have described neo-hyaline cartilage tissue formation as gene expression of COL2A1 and higher glycosaminoglycan content. 18,36 Furthermore, extracellular matrix proteins (e.g., ACAN, DCN, COMP, and HAPLN1) are highly expressed in human cartilage and human articular chondrocytes. 24,26,37 In our studies, both cell types respond to hypoxia by enhancing the expression of several chondrogenic markers including SOX9, HAPLN1, and COMP, but also HIST2H4 and HIF1A.…”

Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF‐β Signaling Pathway

“…However, repetitive mechanical loading and many pathologic factors can cause cartilage damage in the general and athletic populations [ 4 , 5 ]. The cartilage lesion patients usually suffered from pain, swelling, and joint locking [ 6 ], which eventually lead to progressive damage and degenerative diseases, namely, osteoarthritis (OA) which is the leading cause of physical disability [ 7 ].…”

Intra-articular injection of N-acetylglucosamine and hyaluronic acid combined with PLGA scaffolds for osteochondral repair in rabbits

“…Shikhman et al proved that intramuscular injections of GlcNAc provide better chondroprotective and anti-inflammatory activity than HA in an anterior cruciate ligament transection model of OA using rabbits [13, 19]. In addition, our previous study demonstrated that intra-articular administration of GlcNAc promoted the repair of full-thickness articular cartilage defects in a rabbit knee joint model [20]. However, HA is another signal we used to compare osteochondral regeneration with GlcNAc.…”

“…In our previous study, intra-articular injection of GlcNAc could only promote the repair of experimental FTAC defects in the rabbit knee joint model [20]. However, lack of support from the scaffolds could cause subchondral bone overgrowth [24, 25].…”