Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis

Abstract

The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p < 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p < 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p < 0.001; p < 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p < 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint.