Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis

Abstract

NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo.

Effects of intra‐articular hyaluronic acid associated to Chitlac (arty‐duo®) in a rat knee osteoarthritis model

“…OA animal models have a distinct molecular pathophysiology that might promote the translation of disease‐modifying OA therapies from preclinical to clinical trials. Among these models, the DMM model has demonstrated to reproduce the changes observed in clinical settings and be more reliable than other surgical techniques, also mimicking OA that occurs in ageing . Additionally, DMM surgery is highly reproducible, induces OA with a slow progression, with moderate to severe lesions and minimal iatrogenic damage .…”

“…Among these models, the DMM model has demonstrated to reproduce the changes observed in clinical settings and be more reliable than other surgical techniques, also mimicking OA that occurs in ageing. 15,26,36,37 Additionally, DMM surgery is highly reproducible, induces OA with a slow progression, with moderate to severe lesions and minimal iatrogenic damage. 26,36,37 As observed by Glasson et al, 26 DMM induces an OA whose severity progresses from mild-Àmoderate to moderate-Àsevere, with lesions on the central weight bearing area of the joint.…”

“…Although many preclinical and clinical studies evaluating the efficacy and safety of HA, showed that it is an established treatment for knee OA, its rapid clearance and the short residency time in joint cavity limits its use . Nowadays, preclinical research is focusing on the evaluation of new treatments and molecules able to prevent or delay cartilage degradation . In this contest, chitosan seems to be an interesting candidate.…”

“…12 Nowadays, preclinical research is focusing on the evaluation of new treatments and molecules able to prevent or delay cartilage degradation. [14][15] In this contest, chitosan seems to be an interesting candidate. Chitosan, a partially deacetylated derivative from chitin, composed of D-gucosamine and N-acetylglucosamine, is structurally similar to glycosaminoglycans.…”

The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines

“…Moreover, Villermoz et al showed that the overexpression of lumican in a mouse cancer model induced the decrease of Cyclin D1 production, increased apoptosis rate and in turn significantly decreased subcutaneous tumor formation in vivo [42]. Previously, we demonstrated that GlcN and glucosamine-derivative NAPA, were able to stimulate extracellular matrix components, among them also the SLRP lumican and collagens [43,44]. Considering that NCPA is a glucosamine-derivative, very similar to NAPA, we can hypothesize that also NCPA induces lumican production, strengthening the effects on cell cycle and apoptosis that we observed.…”