Glucosamine (Gluc) is a drug used as an anti-inflammatory in moderate forms of knee arthrosis. A further off label use of Gluc is in the anti-aging treatments associated with Polideoxirybonucleotide (PDRN) through intra-dermal injection for a procedure called bio-stimulation. An unexpected effect on cultured dermal fibroblasts, during an experimental study on the gene activation in aesthetic bio-stimulation, was observed. The results have potential application in orthopaedic medical therapy. Fibroblast primary cultures were carried out, seeding cells on a layer of Gluc or PDRN alone or in combination for 24 h. Real Time-PCR was performed to investigate several gene expressions. The MMP13 and the IGF-I gene expression in fibroblast cultures were strongly inhibited after 24 h of incubation with the association of Gluc and PDRN, whereas Gluc and PDRN alone produced a modest inhibition of IGF-I and an activation of MMP13. MMP13 is present in osteoarthritic cartilage and this enzyme plays a significant role in cartilage collagen degradation. IGF1 is involved in growth and development and is successfully used in tissue-engineering for cartilage repair. Based on the reported data, we infer that the association of Gluc and PDRN has a potential application in cartilage therapy. Additional basic science and clinical studies are needed to confirm this preliminary report.