Glucosamine promotes chondrocyte proliferation via the Wnt/β‑catenin signaling pathway

Abstract

The present study investigated the mechanism underlying the effects of glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee cartilage of Sprague-Dawley rats. Chondrocytes were treated with various concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte proliferation were determined using reverse transcription-polymerase chain reaction, western blot analysis and immunohistochemistry. The results indicated that GlcN significantly improved chondrocyte viability, accelerated G1/S transition during progression of the cell cycle and promoted the expression of cell cycle regulatory proteins, including cyclin D1, cyclin-dependent kinase (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation. Furthermore, GlcN upregulated the expression levels of Wnt-4, Frizzled-2 and β-catenin, and downregulated the expression of glycogen synthase kinase-3. GlcN also promoted β-catenin translocation; β-catenin is able to activate numerous downstream target genes, including cyclin D1. To determine the role of the Wnt/β-catenin signaling pathway in chondrocyte proliferation, the Wnt/β-catenin signaling pathway was inhibited using Dickkopf-1 (DKK-1), after which chondrocytes were treated with GlcN. The results demonstrated that the expression levels of β-catenin and cyclin D1 were decreased in chondrocytes treated with DKK-1 and GlcN. These results suggested that GlcN may promote chondrocyte proliferation via the Wnt/β-catenin signaling pathway.

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes

“…Indeed, different studies showed the effects of GS in reducing expression of COX-2, PGE2 production, and inhibiting activation of the NF-κB pathway in human OA chondrocytes and synoviocytes [33][34][35]. Furthermore, GS promoted chondrocyte proliferation and proteoglycan production, while it decreased the expression of inducible form of nitric oxide (iNOS), IL-6, and TNF-α and matrix degrading factors [35][36][37][38].…”

microRNA‐138 induces cell survival and reduces WNT/β‐catenin signaling of osteoarthritis chondrocytes through NEK2

“…The WNT/β‐catenin signaling pathway in an activated state has been demonstrated to be responsible for escalated β‐catenin levels in articular cartilage and could further lead to cartilage changes in OA at the early stage . Cumulative studies have documented the association between the activity of the WNT/β‐catenin signaling pathway and chondrocyte proliferation and differentiation .…”

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

“…In the independent process, the β-catenin undergoes phosphorylation, resulting in ubiquitination and consequent proteasomal degradation. On the other hand, in the β-catenin-dependent pathway, after the binding of Wnt ligands to the transmembrane frizzled (Fzd) receptor, the disheveled protein prevents the phosphorylation of β-catenin inducing the translocation into the nucleus where it stimulates the transcription of anti-apoptotic genes including c-Myc and cyclin D1 [ 48 , 49 ]. Lastly, recent studies seem to show that ERKs might be able to increase rather than decrease the levels of anabolic biomarkers in degenerative human chondrocyte [ 50 , 51 , 52 ].…”

“…Glucosamine (GlcN) is an amino monosaccharide component of glycosaminoglycan (GAG) chains, usually in the form of sulfate or hydrochloride salts derived from the chitin of the exoskeleton of crustaceans and from mushrooms [ 26 ]. Glucosamine promotes the proliferation of human osteoblasts modulating the mTOR pathway and enhancing β-catenin nuclear translocation with consequent activation of cell proliferation via cyclin D1 expression [ 49 , 121 , 137 ].…”